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151. Biomarker Based and Individualized Prognosis for Patients with Mild Cognitive Impairment: Towards a Personalized Medicine Approach for AD

Author: Jens Wiltfang, Pieter Jelle Visser, Sanna-Kaisa Herukka, Oliver Peters, F.R.J. Verhey, Femke H. Bouwman, Andrew Simmons, Patrizia Mecocci, Harald Hampel, Oskar Hansson, Lutz Frölich, Yvonne Freund-Levi, Hilkka Soininen, Inês Baldeiras, Ingrid S. van Maurik, A. de Mendonça, Luiza Spiru, Simon Lovestone, Dina Silva, S. Galluzzi, Philip Scheltens, Wiesje M. van der Flier, Stephanie J.B. Vos, Frederik Barkhof, Charlotte E. Teunissen, Giovanni B. Frisoni, Stéphanie Egret, Åsa K. Wallin, Alzheimer’s Disease Neuroimaging Initiative, Isabel Santana, Sebastian Palmqvist, E. Rüther, Bruno Vellas, Magda Tsolaki, Isabelle Bos, Johannes Kornhuber, Wolfgang Maier, Johannes Berkhof, I. Kloszewska, Flavio Nobili, and Gaël Chételat
Subjects: Oncology, medicine.medical_specialty, business.industry, Internal medicine, Medicine, Biomarker (medicine), Personalized medicine, Cognitive impairment, business
Published: 2019
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152. Smaller medial temporal lobe volumes in individuals with subjective cognitive decline and biomarker evidence of Alzheimer's disease-Data from three memory clinic studies

Author: Wiesje M. van der Flier, José Luis Molinuevo, Sander C.J. Verfaillie, Josef Priller, Frank Jessen, Frederik Barkhof, Lorena Rami, Michael T. Heneka, Oliver Peters, Stefan J. Teipel, Charlotte E. Teunissen, Katharina Buerger, Christoph Laske, Siyao Li, Nina Coll-Padros, Annika Spottke, Emrah Düzel, Xiaochen Hu, Amsterdam Neuroscience - Neurodegeneration, Laboratory Medicine, Radiology and nuclear medicine, Neurology, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
Subjects: Oncology, Male, Epidemiology, pathology [Cognitive Dysfunction], Disease, cerebrospinal fluid [Amyloid beta-Peptides], Neuropsychological Tests, pathology [Alzheimer Disease], 0302 clinical medicine, Cerebrospinal fluid, Germany, Cognitive decline, Netherlands, Aged, 80 and over, Health Policy, Middle Aged, Temporal Lobe, Psychiatry and Mental health, cerebrospinal fluid [Biomarkers], Brain size, Biomarker (medicine), Female, medicine.medical_specialty, tau Proteins, Temporal lobe, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, Aged, Amyloid beta-Peptides, business.industry, Memory clinic, pathology [Temporal Lobe], medicine.disease, 030227 psychiatry, cerebrospinal fluid [tau Proteins], Spain, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Introduction Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. Methods We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona). Analysis of covariance models with samples and cerebrospinal fluid biomarkers as between-subject factors were calculated. Results A significant main effect for AD biomarker (Aβ 42 − > Aβ 42 +) in the left medial temporal lobe (MTL) was found, with the absence of main effects for sample or interaction effects between AD biomarker and sample. This indicates consistent lower left MTL volume across three samples in SCD subjects with abnormal Aβ 42 levels. Discussion Our results support the model that in the presence of AD pathology, SCD corresponds to the late preclinical stage (stage 2 of AD) with smaller MTL volumes.
Published: 2019
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153. A combined miRNA-piRNA signature to detect Alzheimer's disease

Author: Walter Maetzler, Mathis Synofzik, Claudia Schulte, Pooja Rao, Susanne Burkhardt, Tonatiuh Pena Centeno, Christian Deuschle, Ivana Delalle, Oliver Peters, Gaurav Jain, Andre Fischer, Tea Berulava, Lalit Kaurani, Johannes Kornhuber, Michael Hüll, Brit Mollenhauer, Jens Wiltfang, Anne Stuendl, Wolfgang Maier, Hermann Esselmann, and Anja Schneider
Subjects: 0301 basic medicine, Male, genetics [Alzheimer Disease], Disease, cerebrospinal fluid [Amyloid beta-Peptides], genetics [RNA, Small Interfering], Cohort Studies, 0302 clinical medicine, Epigenetics and behaviour, Germany, genetics [MicroRNAs], RNA, Small Interfering, diagnosis [Alzheimer Disease], Middle Aged, Non-coding RNA, 3. Good health, cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Cognitive Dysfunction], Psychiatry and Mental health, cerebrospinal fluid [Biomarkers], Area Under Curve, Biomarker (medicine), Female, Function and Dysfunction of the Nervous System, Alzheimer’s disease, Adult, Piwi-interacting RNA, cerebrospinal fluid [RNA, Small Interfering], Computational biology, Biology, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, microRNA, medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, cerebrospinal fluid [Peptide Fragments], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Aged, Amyloid beta-Peptides, genetics [Cognitive Dysfunction], RNA, medicine.disease, Microvesicles, Peptide Fragments, MicroRNAs, 030104 developmental biology, diagnosis [Cognitive Dysfunction], cerebrospinal fluid [MicroRNAs], Psychiatric disorders, 030217 neurology & neurosurgery, Biomarkers
Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild–cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.
Published: 2019
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154. P3‐327: NEUROPSYCHIATRIC SYMPTOMS IN AT‐RISK GROUPS FOR AD DEMENTIA AND THEIR RELATION TO AD BIOMARKERS: DATA FROM THE DELCODE STUDY

Author: Lena Sannemann, Frank Jessen, Stefan J. Teipel, Anja Schneider, Katharina Buerger, Annika Spottke, Michael T. Heneka, Josef Priller, Frederic Brosseron, Emrah Düzel, Xiaochen Hu, Christoph Laske, Ingo Kilimann, Jens Wiltfang, Michael Wagner, Oliver Peters, and Klaus Fliessbach
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business, Psychiatry
Published: 2018
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155. F1‐04‐02: ASSOCIATION BETWEEN NEURAL NOVELTY RESPONSES AND CSF BIOMARKERS OF ALZHEIMER'S DISEASE: ANATOMICAL SPECIFICITY AND DEPENDENCE ON ATROPHY

Author: Arturo Cardenas-Blanco, Oliver Speck, Michael T. Heneka, Michael Wagner, Coraline D. Metzger, Peter J. Nestor, Annika Spottke, Anja Schneider, Frank Jessen, Emrah Düzel, Katharina Buerger, David Berron, Stefan J. Teipel, Oliver Peters, Klaus Fliessbach, Josef Priller, Daniel Bittner, and Christoph Laske
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Novelty, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Atrophy, Developmental Neuroscience, Csf biomarkers, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Association (psychology)
Published: 2018
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156. P2‐455: STRUCTURAL INTEGRITY IN SUBJECTIVE COGNITIVE DECLINE, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: RESULTS FROM THE DELCODE STUDY

Author: Anja Schneider, Christoph Laske, Frank Jessen, Jens Wiltfang, Katharina Brueggen, Arturo Cardenas-Blanco, Stefan J. Teipel, Oliver Peters, Peter J. Nestor, Michael Wagner, Martin Dyrba, Katharina Buerger, Annika Spottke, Emrah Düzel, and Josef Priller
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Structural integrity, Disease, Audiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Cognitive impairment, Diffusion MRI
Published: 2018
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157. P3‐366: MULTICENTER RESTING STATE FUNCTIONAL CONNECTIVITY IN PRODROMAL AND DEMENTIA STAGES OF ALZHEIMER'S DISEASE: RESULTS FROM THE DZNE DELCODE STUDY

Author: Josef Priller, Frederic Brosseron, Martin Dyrba, Oliver Peters, Michael T. Heneka, Anja Schneider, Annika Spottke, Emrah Düzel, Michael Wagner, Stefan J. Teipel, Michel J. Grothe, Katharina Buerger, Coraline D. Metzger, and Frank Jessen
Subjects: medicine.medical_specialty, Resting state fMRI, Epidemiology, business.industry, Health Policy, Functional connectivity, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Developmental Neuroscience, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2018
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158. TD‐P‐008: USER EXPERIENCE STUDY WITH TWO LOCATING SYSTEMS IN HOME DEMENTIA CARE

Author: Christina Rösch, Herlind Megges, Oliver Peters, and Silka Dawn Freiesleben
Subjects: Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Nursing, User experience design, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Psychology, business
Published: 2018
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159. P1‐140: A GENERIC LATENT VARIABLE APPROACH FOR MEASURING COGNITIVE RESERVE: PHENOTYPE VALIDATION AND GENETIC ASSOCIATION RESULTS

Author: Lutz Frölich, Alfredo Ramirez, Steffen Wolfsgruber, Maria Carolina Dalmasso, Luca Kleineidam, Johannes Kornhuber, Ozioma C. Okonkwo, Oliver Peters, Michael Wagner, Jens Wiltfang, and Wolfgang Maier
Subjects: 0303 health sciences, Epidemiology, Health Policy, Latent variable, Computational biology, Biology, Phenotype, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, 030217 neurology & neurosurgery, 030304 developmental biology, Cognitive reserve, Genetic association
Published: 2018
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160. P4‐142: HOW RELATIONSHIP DYNAMICS BETWEEN PERSONS WITH DEMENTIA AND CAREGIVERS REGARDING SUBJECTIVE TECHNOLOGICAL AFFINITY WITH LOCATING SYSTEMS PLAY OUT OVER TIME

Author: Christina Rösch, Herlind Megges, Silka Dawn Freiesleben, and Oliver Peters
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2018
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161. P2‐447: MICROSTRUCTURAL CHANGES IN ALZHEIMER'S DISEASE, MILD COGNITIVE IMPAIRMENT, AND SUBJECTIVE COGNITIVE DECLINE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: A TBSS ANALYSIS OF DELCODE DATA

Author: Josef Priller, Annika Spottke, Emrah Düzel, Arturo Cardenas-Blanco, Jens Wiltfang, Oliver Peters, Anja Schneider, Peter J. Nestor, Frank Jessen, Katharina Buerger, Stefan J. Teipel, Jan Oliver Kuper-Smith, Christoph Laske, Katharina Brueggen, and Martin Dyrba
Subjects: 0303 health sciences, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Audiology, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Cognitive impairment, 030217 neurology & neurosurgery, 030304 developmental biology, Diffusion MRI
Published: 2018
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162. P3‐289: HARMONIZATION OF SCD OPERATIONALIZATION ACROSS DIFFERENT MEMORY CLINIC SETTINGS: THE EURO‐SCD STUDY

Author: Rosalinde E.R. Slot, Josef Priller, Frank Jessen, Marcel Daamen, Oliver Peters, Alexander Drzezga, Michael T. Heneka, Wiesje M. Flier, Katharina Buerger, Christoph Laske, Charlotte E. Teunissen, José Luis Molinuevo, Michael Wagner, Femke H. Bouwman, Steffen Wolfsgruber, Sietske A.M. Sikkes, Stefan J. Teipel, Linda M.P. Wesselman, Henning Boecker, Lorena Rami, Nina Coll-Padros, Annika Spottke, and Emrah Düzel
Subjects: Operationalization, Epidemiology, business.industry, Health Policy, Memory clinic, Harmonization, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Clinical psychology
Published: 2018
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163. Prevalence of the apolipoprotein E E4 allele in amyloid B positive subjects across the spectrum of Alzheimer's disease

Author: Dong Young Lee, Vincent Camus, Sudesh Prabhakar, Anne M. Fagan, Aleksandra Klimkowicz-Mrowiec, Julius Popp, Frans R.J. Verhey, Victor L. Villemagne, David J. Brooks, Susan M. Landau, Kewei Chen, Johannes Kornhuber, Duk L. Na, Linda J C van Waalwijk van Doorn, Mony J. de Leon, Ann D. Cohen, Charlotte E. Teunissen, Eloy Rodríguez-Rodríguez, Erik Stomrud, Philip Scheltens, Wiesje M. van der Flier, Adrian Ivanoiu, Anders Wallin, Eckart Rüther, Adam S. Fleisher, Isabel Santana, Ramesh Kandimalla, Tormod Fladby, Åsa K. Wallin, Peter Johannsen, Stefan Förster, Sang W. Seo, Gaël Chételat, Koen Van Laere, Ina S. Almdahl, Mark M. Mintun, Dag Aarsland, Sanna-Kaisa Herukka, Harald Hampel, Magda Tsolaki, Henrik Zetterberg, Kristian Steen Frederiksen, John C. Morris, David A. Wolk, Marie Sarazin, Hilkka Soininen, Catherine M. Roe, Sebastiaan Engelborghs, Juha O. Rinne, Hanne Struyfs, Daniel Alcolea, Pieter Jelle Visser, Oliver Peters, Willemijn J. Jansen, Alberto Lleó, Bart N.M. van Berckel, Kiran Dip Gill, Arto Nordlund, Jens Wiltfang, Kaj Blennow, Timo Grimmer, Johannes Schröder, Pauline Aalten, Colin Groot, Pascual Sánchez-Juan, Jan Marcusson, Inês Baldeiras, Mark A. van Buchem, Niklas Mattsson, Christopher C. Rowe, Rik Ossenkoppele, Wolfgang Maier, Agneta Nordberg, Rik Vandenberghe, William E. Klunk, Hanne M. Møllergård, José Luis Molinuevo, Stephanie J.B. Vos, Olymbia Gkatzima, Alexander Drzezga, Oskar Hansson, Lorena Rami, Giovanni B. Frisoni, Karen M. Rodrigue, Olga Meulenbroek, Barbara Mroczko, Marcel M. Verbeek, Juan Fortea, Gil D. Rabinovici, William J. Jagust, Yvonne Freund-Levi, Luiza Spiru, Gunhild Waldemar, Catarina R. Oliveira, Enrica Cavedo, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Frisoni, Giovanni, Popp, Julius, Neurology, Amsterdam Neuroscience - Neurodegeneration, Laboratory Medicine, Radiology and nuclear medicine, APH - Personalized Medicine, and APH - Methodology
Subjects: 0301 basic medicine, Apolipoprotein E, Male, NATIONAL INSTITUTE, Neurology, Epidemiology, Apolipoprotein E4, LONGITUDINAL COHORT, Disease, metabolism [Cognitive Dysfunction], ddc:616.89, 0302 clinical medicine, Prevalence, Geographical location, genetics [Apolipoprotein E4], APOE GENOTYPE, Health Policy, GLUCOSE-METABOLISM, CEREBROSPINAL-FLUID BIOMARKERS, Alzheimer's disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Europe, Psychiatry and Mental health, cerebrospinal fluid [Biomarkers], Biomarker (medicine), lipids (amino acids, peptides, and proteins), Female, Sex, ASSOCIATION WORKGROUPS, metabolism [Alzheimer Disease], APOE, medicine.medical_specialty, Amyloid, CSF BIOMARKERS, metabolism [Amyloid beta-Peptides], CSF, ta3112, Education, 03 medical and health sciences, Cellular and Molecular Neuroscience, Age, Developmental Neuroscience, Alzheimer Disease, Internal medicine, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, Allele, OLDER-ADULTS, Biology, Alleles, Aged, Amyloid beta-Peptides, business.industry, Mild cognitive impairment, medicine.disease, nervous system diseases, 030104 developmental biology, Endocrinology, PET, Positron-Emission Tomography, ddc:618.97, Subjective cognitive decline, DIAGNOSTIC GUIDELINES, Human medicine, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P
Published: 2018
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164. P4‐068: LEVELS OF THE ASTROCYTE‐DERIVED PROTEINS GFAP AND S100B IN THE CEREBROSPINAL FLUID OF HEALTHY INDIVIDUALS AND ALZHEIMER'S DISEASE PATIENTS AT DIFFERENT DISEASE STAGES

Author: Annika Spottke, Emrah Düzel, Carola G. Schipke, Frank Jessen, Michael Wagner, Michael T. Heneka, Anja Schneider, Katharina Buerger, Felix Menne, Jens Wiltfang, Stefan J. Teipel, Oliver Peters, Laske Christoph, Frederic Brosseron, and Josef Priller
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Disease stages, Health Policy, Disease, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cerebrospinal fluid, medicine.anatomical_structure, Developmental Neuroscience, Healthy individuals, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Astrocyte
Published: 2018
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165. P1‐379: CORTICAL THINNING IN SUBJECTIVE COGNITIVE DECLINE WITH AND WITHOUT AD PATHOLOGY: DATA FROM THE DELCODE STUDY

Author: Frank Jessen, Christoph Laske, Stefan J. Teipel, Dix Meiberth, Josef Priller, Michael T. Heneka, Anja Schneider, Annika Spottke, Oliver Peters, Katharina Buerger, Michael Wagner, Jens Wiltfang, Frederic Brosseron, Ingo Kilimann, Ann-Katrin Schild, Klaus Fliessbach, Xiaochen Hu, and Emrah Düzel
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Cortical thinning, Audiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business
Published: 2018
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166. P3‐212: CORRELATING NEUROPSYCHOLOGICAL TESTS WITH CEREBROSPINAL FLUID TO DISCRIMINATE AD FROM DEPRESSION

Author: Manuel Fuentes, Felix Menne, Arne Klostermann, and Oliver Peters
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Neuropsychology, Gastroenterology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Depression (differential diagnoses)
Published: 2018
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167. P1‐028: OCCUPATIONAL COGNITIVE REQUIREMENTS ARE AN IMPORTANT PROXY MEASURE OF COGNITIVE RESERVE: EVIDENCE FROM THE AGECODE AND DELCODE STUDIES

Author: Sandra Roeske, Josef Priller, Alfredo Ramirez, Michael Wagner, Oliver Peters, Jens Wiltfang, Frank Jessen, Emrah Düzel, Anja Schneider, Steffen Wolfsgruber, Annika Spottke, Peter J. Nestor, Luca Kleineidam, Laske Christoph, Ozioma C. Okonkwo, Katharina Buerger, Steffi G. Riedel-Heller, Michael T. Heneka, Martin Scherer, Michael Ewers, Linn Zulka, and Stefan J. Teipel
Subjects: 0303 health sciences, Epidemiology, Health Policy, Measure (physics), Cognition, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Proxy (statistics), Psychology, 030217 neurology & neurosurgery, 030304 developmental biology, Cognitive psychology, Cognitive reserve
Published: 2018
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168. TD‐P‐005: HOW RELATIONSHIP DYNAMICS BETWEEN PERSONS WITH DEMENTIA AND CAREGIVERS REGARDING SUBJECTIVE TECHNOLOGICAL AFFINITY WITH LOCATING SYSTEMS PLAY OUT OVER TIME

Author: Oliver Peters, Christina Rösch, Silka Dawn Freiesleben, and Herlind Megges
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Dynamics (music), Health Policy, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Psychology, medicine.disease, Developmental psychology
Published: 2018
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169. O1‐08‐05: MILD NEUROCOGNITIVE DISORDER IN DSM‐5: BALANCING SENSITIVITY AND SPECIFICITY BY USING OPERATIONAL CRITERIA

Author: Steffen Wolfsgruber, Oliver Peters, Michael Wagner, Johannes Kornhuber, Wolfgang Maier, Jens Wiltfang, Alexandra Polcher, and Lutz Frölich
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Audiology, DSM-5, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Mild neurocognitive disorder, Neurology (clinical), Sensitivity (control systems), Geriatrics and Gerontology, business
Published: 2018
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170. P3‐591: A GERMAN VERSION OF THE LIFETIME OF EXPERIENCES QUESTIONNAIRE (LEQ) TO MEASURE COGNITIVE RESERVE: VALIDATION RESULTS FROM THE DELCODE STUDY

Author: Oliver Peters, Frank Jessen, Josef Priller, Luca Kleineidam, Annika Spottke, Jens Wiltfang, Emrah Düzel, Katharina Buerger, Anja Schneider, Michael Wagner, Elke Kalbe, Christoph Laske, Michael T. Heneka, Alfredo Ramirez, Michael Ewers, Steffen Wolfsgruber, Ozioma C. Okonkwo, Linn Zulka, Stefan J. Teipel, Sandra Roeske, and Peter J. Nestor
Subjects: Epidemiology, Health Policy, 05 social sciences, Applied psychology, Measure (physics), 050109 social psychology, 050105 experimental psychology, language.human_language, German, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, language, 0501 psychology and cognitive sciences, Neurology (clinical), Geriatrics and Gerontology, Psychology, Cognitive reserve
Published: 2018
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171. 8. Medikamentöse Therapie

Author: Oliver Peters, Timo Grimmer, Peter Häussermann, and Cornel C. Sieber
Published: 2018
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172. Multicenter Resting State Functional Connectivity in Prodromal and Dementia Stages of Alzheimer's Disease

Author: Josef Priller, Michael Wagner, Michael T. Heneka, Anja Schneider, Laura Dobisch, Felix Menne, Alexandra Polcher, Annika Spottke, Emrah Düzel, Stefan J. Teipel, Eike Jakob Spruth, Christiana Franke, Martin Dyrba, Klaus Fliebach, Cihan Catak, René Thyrian, Dominik Diesing, Katharina Brueggen, Manuela Thelen, Ingo Kilimann, Frederic Brosseron, Frank Jessen, Oliver Peters, Katharina Buerger, Coraline D. Metzger, and Barbara Kofler
Subjects: Male, cerebrospinal fluid [Amyloid beta-Peptides], Logistic regression, Correlation, 0302 clinical medicine, Germany, Image Processing, Computer-Assisted, diagnostic imaging [Dementia], Cognitive decline, Default mode network, General Neuroscience, 05 social sciences, Brain, General Medicine, amyloid beta-protein (1-42), Magnetic Resonance Imaging, cerebrospinal fluid [Alzheimer Disease], Psychiatry and Mental health, Clinical Psychology, blood [Oxygen], Biomarker (medicine), Female, medicine.medical_specialty, Rest, Prodromal Symptoms, physiopathology [Alzheimer Disease], 050105 experimental psychology, 03 medical and health sciences, Physical medicine and rehabilitation, Alzheimer Disease, Journal Article, medicine, Dementia, Humans, 0501 psychology and cognitive sciences, ddc:610, cerebrospinal fluid [Peptide Fragments], diagnostic imaging [Brain], Aged, Amyloid beta-Peptides, Resting state fMRI, business.industry, amyloid beta-protein (1-40), medicine.disease, Peptide Fragments, Oxygen, Observational study, Geriatrics and Gerontology, business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery
Abstract: BACKGROUND: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer's disease (AD).OBJECTIVE: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD.METHODS: We determined rs-fMRI functional connectivity based on Pearson's correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls. We used data of 247 participants of the prospective DELCODE study, a longitudinal multicenter observational study, imposing a unified fMRI acquisition protocol across sites. We determined cross-validated discrimination accuracy based on penalized logistic regression to account for multicollinearity of predictors.RESULTS: Resting state functional connectivity reached significant cross-validated group discrimination only for the comparison of AD dementia cases with healthy controls, but not for the other diagnostic groups. AD dementia cases showed alterations in a large range of intrinsic resting state networks, including the default mode and salience networks, but also executive and language networks. When groups were stratified according to their CSF amyloid status that was available in a subset of cases, diagnostic accuracy was increased for amyloid positive mild cognitive impairment cases compared with amyloid negative controls, but still inferior to the accuracy of hippocampus volume.CONCLUSION: Even when following a strictly harmonized data acquisition protocol and rigorous scan quality control, widely used connectivity measures of multicenter rs-fMRI do not reach levels of diagnostic accuracy sufficient for a useful biomarker in prodromal stages of AD.
Published: 2018
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173. VPTMAGAZIN meets ... Die Physiotutors

Author: Tanja Hergel and Oliver Peters
Abstract: ZusammenfassungUnser Presse- und Öffentlichkeitsarbeitsteam Tanja Hergel und Oliver Peters haben sich mit den „YouTube-Stars“ unserer Branche getroffen und ein kurzes Interview geführt. Andreas Heck und Kai Sigel betreiben sehr erfolgreich den YouTube-Channel Physiotutors und vermitteln mit ihren Beiträgen physiotherapeutisches Fachwissen an Kolleginnen und Kollegen aus aller Welt …
Published: 2019
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174. P3-016: BUPROPION FOR THE TREATMENT OF APATHY IN ALZHEIMER'S DISEASE: A MULTICENTER RANDOMIZED CONTROLLED TRIAL

Author: Annika Spottke, Oliver Peters, Rolf Horn, Christine A. F. von Arnim, Lutz Frölich, Josef Priller, Stefan J. Teipel, Richard Dodel, Franziska Maier, Anja Schneider, Katharina Buerger, Johannes Kornhuber, Stefan Klöppel, Jens Wiltfang, Christoph Laske, Frank Jessen, and Andreas Fellgiebel
Subjects: Bupropion, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, law.invention, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Randomized controlled trial, law, 030225 pediatrics, Internal medicine, Medicine, Apathy, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Published: 2019
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175. P3-447: MINOR NEUROPSYCHOLOGICAL DEFICITS IN COGNITIVELY NORMAL OLDER INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE: RESULTS FROM THE DELCODE STUDY

Author: Luca Kleineidam, Michael T. Heneka, Josef Priller, Michael Wagner, Anja Schneider, Stefan J. Teipel, Michael Ewers, Oliver Peters, Katharina Buerger, Frank Jessen, Jens Wiltfang, Annika Spottke, Steffen Wolfsgruber, and Christoph Laske
Subjects: 0303 health sciences, Epidemiology, Health Policy, Neuropsychology, Minor (academic), 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, Psychology, 030217 neurology & neurosurgery, 030304 developmental biology, Clinical psychology
Published: 2019
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176. P1-407: RELATIONSHIP BETWEEN GLOBAL CONNECTIVITY, AMYLOID AND TAU IN DIFFERENT STAGES DURING THE DEVELOPMENT OF ALZHEIMER'S DISEASE AS DEMONSTRATED IN THE DZNE DELCODE COHORT

Author: Josef Priller, Frank Jessen, Alexandra Polcher, Eike Jakob Spruth, Alfredo Ramirez, Laura Dobisch, Felix Menne, Steffen Wolfsgruber, Ingo Frommann, Anja Schneider, Klaus Fliessbach, Manuel Fuentes, Martina Buchmann, Manuela Thelen, Ingo Kilimann, Stefan J. Teipel, Michel J. Grothe, Jens Wiltfang, Martin Dyrba, Christoph Laske, Michael T. Heneka, Cihan Catak, Oliver Peters, Barbara Kofler, Frederic Brosseron, Katharina Bürger, Claudia Bartels, Christiana Franke, Daniel Bittner, Annika Spottke, Emrah Düzel, Xiaochen Hu, Sandra Roeske, Michael Wagner, and Coraline D. Metzger
Subjects: Oncology, medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, Disease, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, 030225 pediatrics, Internal medicine, Cohort, medicine, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Published: 2019
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177. P3-361: EXPLAINABLE CONVOLUTIONAL NETWORKS AND MULTIMODAL IMAGING DATA: THE NEXT STEP TOWARDS USING ARTIFICIAL INTELLIGENCE AS DIAGNOSTIC TOOL FOR EARLY DETECTION OF ALZHEIMER'S DISEASE

Author: Michael Wagner, Klaus Fliessbach, Josef Priller, Emrah Düzel, Michael T. Heneka, Martin Dyrba, Eman N. Marzban, Delcode Study Groups, Christoph Laske, Jens Wiltfang, Adni, Anja Schneider, Annika Spottke, Frank Jessen, Oliver Peters, Stefan J. Teipel, Ingo Kilimann, and Katharina Buerger
Subjects: Multimodal imaging, Epidemiology, business.industry, Computer science, Health Policy, Early detection, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology (clinical), Artificial intelligence, Geriatrics and Gerontology, business
Published: 2019
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178. IC-P-028: PATTERNS OF INCREASED AND DECREASED PRECUNEUS FUNCTIONAL CONNECTIVITY IN SCD DEPENDING ON AMYLOID STATUS

Author: Frank Jessen, Oliver Peters, Axel Rominger, Stefan J. Teipel, Bernd J. Krause, Markus Essler, Marcel Daamen, Lukas Scheef, Anja Schneider, Klaus Fließbach, Ralph Buchert, Shumei Li, Emrah Düzel, Henning Boecker, Katharina Buerger, Florian Gaertner, Annika Spottke, Matthias Reimold, Holger Amthauer, and Christoph Laske
Subjects: Amyloid, Epidemiology, Chemistry, Health Policy, Functional connectivity, Precuneus, Psychiatry and Mental health, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Neuroscience
Published: 2019
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179. P2-359: CORTICAL AMYLOID BURDEN CORRELATES WITH ATROPHY OF THE POSTERIOR PART OF THE NUCLEUS BASALIS MEYNERT IN AMYLOID-POSITIVE SCD

Author: Oliver Peters, Markus Essler, Klaus Fliessbach, Marcel Daamen, Bernd J. Krause, Annika Spottke, Axel Rominger, Florian Gaertner, Anja Schneider, Michel J. Grothe, Matthias Reimold, Lukas Scheef, Ralph Buchert, Emrah Düzel, Shumei Li, Katharina Buerger, Stefan J. Teipel, Frank Jessen, Henning Boecker, Holger Amthauer, and Christoph Laske
Subjects: Pathology, medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, Nucleus basalis, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Atrophy, Developmental Neuroscience, Medicine, Amyloid burden, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2019
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180. IC-P-016: CORTICAL AMYLOID BURDEN CORRELATES WITH ATROPHY OF THE POSTERIOR PART OF THE NUCLEUS BASALIS MEYNERT IN AMYLOID-POSITIVE SCD

Author: Lukas Scheef, Marcel Daamen, Michel J. Grothe, Shumei Li, Florian Gaertner, Oliver Peters, Holger Amthauer, Ralph Buchert, Katharina Buerger, Axel Rominger, Stefan J. Teipel, Bernd J. Krause, Klaus Fliessbach, Anja Schneider, Markus Essler, Christoph Laske, Matthias Reimold, Annika Spottke, Emrah Düzel, Frank Jessen, and Henning Boecker
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2019
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181. IC-P-122: ALTERATIONS OF INTRINSIC CONNECTIVITY IN POSTERIOR DEFAULT MODE NETWORK ACROSS AT RISK STAGES OF ALZHEIMER'S DEMENTIA

Author: Katharina Bürger, Christoph Laske, Oliver Peters, Jens Wiltfang, Hwee Ling Lee, Annika Spottke, Emrah Düzel, Xiaochen Hu, Stefan J. Teipel, Josef Priller, and Frank Jessen
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Alzheimer s dementia, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, Default mode network
Published: 2019
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182. Akzeptanz der Demenzdiagnostik bei stationären, geriatrischen Patienten

Author: Ralph Buchert, Herlind Megges, Melanie Estrella, Jochen B. Fiebach, Elisabeth Steinhagen-Thiessen, Anna Roberts, Anja Mäurer, and Oliver Peters
Subjects: medicine.medical_specialty, Health (social science), 030214 geriatrics, Geriatrics gerontology, business.industry, medicine.disease, 03 medical and health sciences, Issues, ethics and legal aspects, 0302 clinical medicine, Patient satisfaction, Patient information, medicine, Physical therapy, Dementia, Dementia diagnosis, Geriatrics and Gerontology, Cognitive impairment, business, Gerontology, 030217 neurology & neurosurgery
Abstract: Hintergrund Die Zahl der Demenzkranken steigt, auch in Krankenhausern. Fur die Diagnose stehen neue Verfahren zur Verfugung, die Einstellung der Patienten hierzu ist jedoch unbekannt.
Published: 2016
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183. Chiral recognition of enantiomeric isobornyl methacrylate-containing hydrogels with α -cyclodextrin

Author: Helmut Ritter and Oliver Peters
Subjects: chemistry.chemical_classification, Polymers and Plastics, Cyclodextrin, 010405 organic chemistry, Chemistry, Organic Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Polymer chemistry, Self-healing hydrogels, Materials Chemistry, Organic chemistry, Isobornyl methacrylate, Enantiomer
Published: 2015
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184. Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer's disease

Author: Frank Jessen, Lutz Frölich, Johannes Kornhuber, Oliver Peters, Alexander Kurz, Klaus Schmidtke, Birgitt Wiese, Isabella Heuser, Jens Wiltfang, Eckart Rüther, Hans-Jürgen Möller, Manuel Fuentes, Lisa Katharina Joachim, Christian Luckhaus, Wolfgang Maier, Johannes Pantel, and Michael Hüll
Subjects: Galantamine-CR, medicine.drug_class, Disease, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Memantine, Galantamine, medicine, Dementia, ddc:610, 030212 general & internal medicine, Antagonist, Featured Article, Alzheimer's disease, medicine.disease, Acetylcholinesterase, 3. Good health, Psychiatry and Mental health, Regimen, chemistry, Acetylcholinesterase inhibitor, Combination treatment, Neurology (clinical), Function and Dysfunction of the Nervous System, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Introduction: Several studies have tested the N-methyl-D-aspartate–receptor antagonist memantine as an add-on to pre-existing treatment with acetylcholinesterase inhibitors. The objective of this study was to evaluate the efficacy and safety of a combined memantine and galantamine-CR de novo regimen compared with galantamine-CR only treatment in never treated patients with mild-to-moderate Alzheimer's disease (AD). Methods: Antidementia drug–naïve participants (n = 232) with probable, mild-to-moderate AD, and mini-mental state examination scores between 15 and 26 (inclusive) were randomized to receive either 20 mg/day memantine plus 24 mg/day galantamine-CR or 24 mg/day galantamine-CR plus placebo in a 52-week, prospective, double-blind, controlled trial. The primary outcome measurement was the change on the Alzheimer's disease assessment scale-cognition score. Secondary measures comprised the Alzheimer's Disease Cooperative Study-activities of daily living inventory and the clinical dementia rating. Results: At the end of the trial, there were no statistically significant differences between the galantamine-CR/memantine combination and galantamine-CR only group in primary and secondary outcome measurements. The incidence and the severity of adverse events were similar between the groups. Discussion: In this trial, memantine in combination with galantamine-CR did not show an advantage with respect to cognition, function, and behavior in previously never treated patients with mild-to-moderate AD. There were no significant differences in tolerability and safety between the groups. Thus, a de novo combination treatment results in no significant improvement in disease progression (current controlled trials number: NCT01921972).
Published: 2015
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185. Validation of the Erlangen Score Algorithm for the Prediction of the Development of Dementia due to Alzheimer’s Disease in Pre-Dementia Subjects

Author: Johannes Kornhuber, Jens Wiltfang, Malgorzata Knapik-Czajka, John Q. Trojanowski, Jon B. Toledo, Piotr Lewczuk, Oliver Peters, and Leslie M. Shaw
Subjects: tau Proteins, Kaplan-Meier Estimate, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Alzheimer Disease, medicine, Humans, Dementia, Longitudinal Studies, Phosphorylation, Cognitive impairment, Aged, Proportional Hazards Models, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Laboratory methods, Amyloid beta-Peptides, Clinical neurochemistry, Proportional hazards model, business.industry, General Neuroscience, General Medicine, Middle Aged, Prognosis, medicine.disease, Peptide Fragments, Psychiatry and Mental health, Clinical Psychology, Asymptomatic Diseases, Disease Progression, Geriatrics and Gerontology, Alzheimer's disease, business, Algorithm, Algorithms, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background: In previous studies, a dichotomous stratification of subjects into "cerebrospinal fluid (CSF) normal" and "CSF pathologic" was used to investigate the role of biomarkers in the prediction of progression to dementia in pre-dementia/mild cognitive impairment subjects. With the previously published Erlangen Score Algorithm, we suggested a division of CSF patterns into five groups, covering all possible CSF result combinations based on the presence of pathologic tau and/or amyloid-{beta} CSF values. Objective: This study aimed to validate the Erlangen Score diagnostic algorithm based on the results of biomarkers analyses obtained in different patients cohorts, with different pre-analytical protocols, and with different laboratory analytical platforms. Methods: We evaluated the algorithm in two cohorts of pre-dementia subjects: the US-Alzheimer's Disease Neuroimaging Initiative and the German Dementia Competence Network. Results: In both cohorts, the Erlangen scores were strongly associated with progression to Alzheimer's disease. Neither the scores of the progressors nor the scores of the non-progressors differed significantly between the two projects, in spite of significant differences in the cohorts, laboratory methods, and the samples treatment. Conclusions: Our findings confirm the utility of the Erlangen Score algorithm as a useful tool in the early neurochemical diagnosis of Alzheimer's disease.
Published: 2015
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186. Auf hohem Niveau: Risiko Gedächtnissorgen

Author: M. A. Marc Borner, Manuel Fuentes Casan, and Oliver Peters
Subjects: business.industry, Medicine, business
Published: 2015
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187. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease

Author: Josef Priller, Daniel Janowitz, Johannes Levin, Miguel Ángel Araque Caballero, Henning Boecker, Christiana Franke, Anne M. Fagan, Frank Jessen, Martin Dichgans, Jens Wiltfang, Michael T. Heneka, Christian Haass, Michael W. Weiner, Alison Goate, Peter Falkai, Daniel Bittner, Felix Menne, Marc Suárez-Calvet, Anja Schneider, Barbara Kofler, Oliver Peters, Eike Jakob Spruth, Marco Duering, Michael Wagner, Stefan J. Teipel, Colin L. Masters, Oliver Speck, Robert Perneczky, Peter J. Nestor, Tammie L.S. Benzinger, Coraline D. Metzger, Frederic Brosseron, Jae-Hong Lee, Manuel Fuentes, Christine Westerteicher, Jasmeer P. Chhatwal, Cihan Catak, Katrina L. Paumier, Claudia Bartels, Martin N. Rossor, Adrian Danek, Stephen Salloway, Mathias Jucker, Ingo Kilimann, Klaus Fliessbach, Peter R. Schofield, Alfredo Ramirez, Nicolai Franzmeier, Annika Spottke, Emrah Düzel, Steffen Wolfsgruber, Katharina Buerger, Christoph Laske, John C. Morris, Randall J. Bateman, and Michael Ewers
Subjects: Male, Aging, Alzheimer's Disease, Brain mapping, Imaging, 0302 clinical medicine, Medicine, Aetiology, 10. No inequality, Cognitive reserve, FUNCTIONAL CONNECTIVITY, 11 Medical And Health Sciences, Frontal Lobe, CORTICAL HUBS, genetics [Amyloid beta-Protein Precursor], BRAIN RESERVE, Biomedical Imaging, LOW-FREQUENCY, Alzheimer's disease, Clinical Trials and Supportive Activities, Basic Behavioral and Social Science, 03 medical and health sciences, PSEN1 protein, human, WORKING-MEMORY, Clinical Research, Alzheimer Disease, Humans, Cognitive Dysfunction, OLDER-ADULTS, Science & Technology, Working memory, physiology [Functional Laterality], medicine.disease, 030104 developmental biology, Mutation, Dementia, Neurosciences & Neurology, Neurology (clinical), Neuroscience, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery, 0301 basic medicine, diagnostic imaging [Cognitive Dysfunction], genetics [Alzheimer Disease], Neurodegenerative, Medical and Health Sciences, Functional Laterality, etiology [Cognitive Dysfunction], memory, Amyloid beta-Protein Precursor, 2.1 Biological and endogenous factors, Cognitive decline, Brain Mapping, complications [Alzheimer Disease], genetics [Presenilin-1], Middle Aged, cognitive reserve, Magnetic Resonance Imaging, Frontal lobe, IMAGING BIOMARKERS, Neurological, Female, physiology [Nerve Net], Life Sciences & Biomedicine, Alzheimer’s disease, Adult, Clinical Neurology, genetics [Mutation], genetics [Presenilin-2], dementia biomarkers, 17 Psychology And Cognitive Sciences, Imaging, Three-Dimensional, diagnostic imaging [Frontal Lobe], Behavioral and Social Science, HIPPOCAMPAL FUNCTION, Presenilin-2, Acquired Cognitive Impairment, Presenilin-1, Journal Article, Effects of sleep deprivation on cognitive performance, ddc:610, Neurology & Neurosurgery, Resting state fMRI, business.industry, diagnostic imaging [Nerve Net], PSEN2 protein, human, Psychology and Cognitive Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Original Articles, Brain Disorders, PHYSICAL-ACTIVITY, MEMORY VARIANCE, Three-Dimensional, resting state connectivity, Nerve Net, business
Abstract: The neural basis of reserve capacity in Alzheimer’s disease is yet to be fully determined. Franzmeier et al. show that greater left frontal hub connectivity within the fronto-parietal control network is associated with greater resilience of cognitive performance during the early stages of autosomal dominant and sporadic Alzheimer’s disease., Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer’s disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer’s disease is at least partially attributable to higher left frontal cortex-hub connectivity.
Published: 2018
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188. PLCG2 Protective Variant p.P522R Modulates Tau Pathology and Disease Progression in Patients with Mild Cognitive Impairment

Author: Michael T. Heneka, Michael Hüll, Alfredo Ramirez, Sven J. van der Lee, Pamela V. Martino Adami, Anja Schneider, Wiesje M. van der Flier, Antonio González-Pérez, Eckart Rüther, Agustín Ruiz, Frank Jessen, Martin Scherer, Leonie Weinhold, Jean-François Dartigues, Henne Holstege, Mercè Boada, Thomas Próchnicki, Itziar de Rojas, Reinhard Heun, Frederic Brosseron, Ana Espinosa, Piotr Lewczuk, Laura Madrid-Márquez, Lutz Frölich, Steffen Wolfsgruber, Matthias Schmid, Holger Wagner-Thelen, Marc Hulsman, Philip Scheltens, Isabel Hernández, Vincent Chouraki, Lluís Tárraga, Johannes Kornhuber, Adela Orellana, Michael Wagner, Oliver Peters, Eicke Latz, Philippe Amouyel, Jens Wiltfang, Claudine Berr, Martijn Huisman, Jean-Charles Lambert, Iris E. Jansen, Wolfgang Maier, Ilker Karaca, Christopher Tzourio, Sergi Valero, Mª Eugenia Sáez, Natasja M. van Schoor, Anne Boland, Jean-François Deleuze, Julius Popp, Najada Stringa, Luca Kleineidam, and Steffi G. Riedel-Heller
Subjects: medicine.medical_specialty, education.field_of_study, 050208 finance, Tau pathology, business.industry, 05 social sciences, Population, Disease progression, Ethics committee, Safety Monitoring Boards, 3. Good health, Family medicine, 0502 economics and business, medicine, In patient, 050207 economics, Cognitive decline, Cognitive impairment, education, business
Abstract: Background: A rare coding variant (rs72824905, p.P522R) conferring protection against the susceptibility to Alzheimer's disease (AD) was recently identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2). Here, we explore the protective nature of this variant with regard to AD pathology indicated by biomarkers, cognitive decline, and potential underlying biological mechanisms. Methods: Association of p.P522R with CSF levels of pTau181, total Tau and Aβ1-42 was assessed in 1,282 patients with mild cognitive impairment (MCI) or AD-dementia syndrome. In addition, the association with longitudinal cognitive decline was tested in 3,010 MCI patients from memory clinic cohorts and 10,100 individuals from population-based studies using latent process linear mixed models. Finally, unsupervised co-trans-regulatory network analysis and biological experiments were conducted. Findings: Carriers of the p.P522R variant showed lower pTau181 levels in CSF compared to non-carriers, specifically in the presence of amyloid pathology. In MCI patients but not in population-based cohorts, the p.P522R variant was associated with slower cognitive decline with an effect size similar to that of APOE-e4. We identified a network of coregulated proteins linking PLCG2 to APOE and TREM2. Finally, in vitro experiments confirmed that inflammasome activation upon phospholipase C stimulation might act downstream of PLCG2. Implication: Our data link the protective effect of p.P522R in PLCG2 to reduced Tau pathology, to a slower cognitive decline in MCI patients and to underlying inflammatory processes. Therapies targeting the enzyme PLCG2 might provide a therapeutic approach for AD. Funding Statement: EU Joint Programme Neurodegenerative Disease Research, Innovative Medicines Initiative 2, Instituto de Salud Carlos III, La Caixa, Grifols SA, German Federal Ministry of Research and Education, Sanofi Laboratories, Fondation pour la Recherche Medicale, Fondation Plan Alzheimer, Stichting Alzheimer Nederland, Stichting VUmc fonds, Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care, Netherlands Organization for Scientific Research (NWO), EMGO+ Research Institute. Declaration of Interests: All authors report no conflict of interest. PL received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, and Roche. JW received honoraria for consulting activities, lectures or advisory board participation from Pfizer, Eli Lilly, Hoffmann-La-Roche, MSD Sharp + Dome, Janssen-Cilag GmbH, Immungenetics AG, Boehringer Ingelheim. LF received honoraria for consulting activities, lectures or advisory board participation from Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, MerckSharpe & Dohme, Novartis, Pfizer, Pharnext, Roche, Schwabe Pharma; he served on Data and Safety Monitoring boards or endpoint committees with Avraham Pharmaceuticals, Axon Neuroscience, Forschungszentrum Julich, Novartis, Pharmatropix. JP received honoraria for consulting activities, lectures or advisory board participation from Fujirebio Europe, Ono Pharma, Eli Lilly, and Nestle Institute of Health Sciences. ARu reports consulting Fees: Landsteiner Genmed, Grifols, Araclon biotech. And Lecture Fees: Araclon Biotech.PA reports personal fees from Servier, Total, Genoscreen, Takeda, Foundation Alzheimer. OP received research funding, consultancy fees or speech honoraria from Axovant, Biogen, Genentech, Lilly, Lundbeck, Novartis, Pharmatrophix, Piramal, Probiodrug, Roche, Takeda and TauRx Pharmaceuticals. MB receives fees or has received for consulting from Lab. Servier, Roche, Lilly, Avid, Bayer, Elan, Janssen, Neuroptix, Sanofi. She receives or has received fees for lectures from Lilly, Nutricia, Roche, Schwabe, Araclon, Esteve, Grifols, Janssen, Novartis, Piramal, Pfizer-Wyett, Servier. She receives fees for being part of the Advisory Board of Lilly and Schwabe. She reports grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, S.A, Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia SRL, Oryzon Genomics, Piramal Imaging Limited, Roche Pharma SA, and Schwabe Farma iberica SLU, all outside the submitted work. She has not received personal compensations from these organizations Ethics Approval Statement: The individual studies were approved by the respective ethics committees.
Published: 2018
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189. Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer’s disease (DELCODE)

Author: Klaus Fliessbach, Annika Spottke, Emrah Düzel, Eike Jakob Spruth, Frank Jessen, Steffen Wolfsgruber, Verena Pross, Oliver Speck, Michael Wagner, Alfredo Ramirez, Katharina Buerger, Oliver Peters, Ingo Kilimann, Jens Wiltfang, Josef Priller, Ruth Vukovich, Henning Boecker, Christoph Laske, Manuel Fuentes, Felix Menne, Cihan Catak, Frederic Brosseron, Michael T. Heneka, Stefan J. Teipel, Daniel Janowitz, Peter J. Nestor, Anja Schneider, Christiana Franke, and Christine Westerteicher
Subjects: 0301 basic medicine, Male, Neurology, psychology [Alzheimer Disease], epidemiology [Cognitive Dysfunction], epidemiology [Alzheimer Disease], diagnostic imaging [Cognitive Dysfunction], genetics [Alzheimer Disease], Neuropsychological Tests, lcsh:RC346-429, 0302 clinical medicine, Cognition, Germany, Longitudinal Studies, Cognitive decline, education.field_of_study, Neuropsychology, Brain, Magnetic Resonance Imaging, 3. Good health, Cerebrospinal fluid, cerebrospinal fluid [Biomarkers], Research Design, Biomarker (medicine), Female, psychology [Cognitive Dysfunction], Apolipoprotein E, Alzheimer’s disease, medicine.medical_specialty, Positron emission tomography, Clinical Dementia Rating, Cognitive Neuroscience, Population, Beta-amyloid 42, lcsh:RC321-571, 03 medical and health sciences, Apolipoproteins E, Magnetic resonance imaging, Alzheimer Disease, Internal medicine, medicine, Journal Article, Dementia, Humans, Cognitive Dysfunction, Family, Genetic Predisposition to Disease, ddc:610, education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, diagnostic imaging [Brain], lcsh:Neurology. Diseases of the nervous system, Aged, business.industry, Research, genetics [Cognitive Dysfunction], Mild cognitive impairment, medicine.disease, 030104 developmental biology, Positron-Emission Tomography, Longitudinal, genetics [Apolipoproteins E], Subjective cognitive decline, Observational study, Neurology (clinical), Amnesia, Tau, business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery, Biomarkers
Abstract: Background Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer’s disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. Methods The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer’s dementia patients, first-degree relatives of patients with Alzheimer’s dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets. Results In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer’s Disease Assessment Scale—cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aβ42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected. Conclusions The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aβ42 concentration. Trial registration German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.
Published: 2018
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190. Association of Cerebral Amyloid-Β Aggregation With Cognitive Functioning in Persons Without Dementia

Author: Myriam Alexander, Steven E. Arnold, Stephanie J.B. Vos, Viviana Lisetti, Gunhild Waldemar, Marzena Zboch, David A. Wolk, Sebastiaan Engelborghs, Sabine Hellwig, Adrian Ivanoiu, José Luis Molinuevo, Duk L. Na, Sebastian Köhler, Elisabeth Kapaki, Catarina R. Oliveira, Enrica Cavedo, Ina S. Almdahl, Karine Madsen, Mark A. Mintun, Frans R.J. Verhey, Juha O. Rinne, John C. Morris, Hanne Struyfs, George P. Paraskevas, Oliver Peters, Ann D. Cohen, Philip Scheltens, Willemijn J. Jansen, Linda J C van Waalwijk van Doorn, Eckart Rüther, Sanna-Kaisa Herukka, Osama Sabri, Mark Forrest Gordon, Yvonne Freund-Levi, Rik Vandenberghe, Lucrezia Hausner, Marie Sarazin, Kristian Steen Frederiksen, Inês Baldeiras, William E. Klunk, Susan M. Landau, Timo Grimmer, Lutz Froelich, Betty M. Tijms, Dong Young Lee, Peter Johannsen, Aleksandra Klimkowicz-Mrowiec, Charlotte E. Teunissen, Kaj Blennow, Mony J. de Leon, Christopher C. Rowe, Alberto Lleó, Uroš Rot, Pascual Sánchez-Juan, Daniel Alcolea, Henryk Barthel, Wiesje M. van der Flier, Olga Meulenbroek, Tomasz Gabryelewicz, Tormod Fladby, Andrew B. Newberg, Åsa K. Wallin, Marcel M. Verbeek, Lucilla Parnetti, Bart N.M. van Berckel, Vincent Mok, Oskar Hansson, Victor L. Villemagne, David J. Brooks, Helmut Hildebrandt, Koen Van Laere, Dag Aarsland, Inez H.G.B. Ramakers, Harald Hampel, Elena Chipi, Henrik Zetterberg, Erik Stomrud, Hilkka Soininen, Juan Fortea, Gil D. Rabinovici, Anders Wallin, Vincent Camus, Gayan Perera, Julius Popp, Pieter Jelle Visser, Magda Tsolaki, Johannes Kornhuber, Anne M. Fagan, Niklas Mattsson, William J. Jagust, Luiza Spiru, Hanne M. Møllergård, Adam S. Fleisher, Isabel Santana, Jens Wiltfang, Jan Marcusson, Alexander Drzezga, Giovanni B. Frisoni, Catherine M. Roe, Mark A. van Buchem, Norman Koglin, Johannes Schröder, Pauline Aalten, Olymbia Gkatzima, Lorena Rami, Wolfgang Maier, Agneta Nordberg, Alexandre de Mendonça, Gerald Novak, Gaël Chételat, Arto Nordlund, Milica G. Kramberger, Rik Ossenkoppele, Barbara Mroczko, Kewei Chen, Eloy Rodríguez-Rodríguez, Stefan Förster, Sang W. Seo, Philipp T. Meyer, Clinical sciences, Neurology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Amyloid Biomarker Study Group, Frisoni, Giovanni, Popp, Julius, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, APH - Methodology, Radiology and nuclear medicine, Laboratory Medicine, and CCA - Imaging and biomarkers
Subjects: 0301 basic medicine, PRECLINICAL ALZHEIMERS-DISEASE, Male, psychology [Alzheimer Disease], physiopathology [Cognitive Dysfunction], cerebrospinal fluid [Amyloid beta-Peptides], physiopathology [Brain], ddc:616.89, 0302 clinical medicine, Reference Values, 10. No inequality, Episodic memory, ta515, Original Investigation, LIFE-SPAN, Medicine(all), Geriatrics, Cerebral Amyloid-β Aggregation, diagnosis [Alzheimer Disease], Brain, Cognition, IMPAIRMENT, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Mental Status and Dementia Tests, Cognitive test, Psychiatry and Mental health, physiopathology [Cognition Disorders], Female, psychology [Cognitive Dysfunction], Alzheimer's disease, BURDEN, APOE, medicine.medical_specialty, Memory, Episodic, psychology [Cognition Disorders], ta3112, physiopathology [Alzheimer Disease], 03 medical and health sciences, AGE, Alzheimer Disease, Internal medicine, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, Cognitive skill, ddc:610, METAANALYSIS, Aged, diagnosis [Cognition Disorders], DECLINE, Amyloid beta-Peptides, business.industry, MEMORY PERFORMANCE, Correction, medicine.disease, ta3124, INDIVIDUALS, 030104 developmental biology, Cross-Sectional Studies, diagnosis [Cognitive Dysfunction], Positron-Emission Tomography, Human medicine, business, Cognition Disorders, 030217 neurology & neurosurgery, dementia
Abstract: Contains fulltext : 190311.pdf (Publisher’s version ) (Closed access) Importance: Cerebral amyloid-beta aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-beta aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score
Published: 2018
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191. Subjective cognitive decline is related to CSF biomarkers of AD in patients with MCI

Author: Johannes Kornhuber, Stefanie Schulz, Eckart Rüther, Michael Hüll, Wolfgang Maier, Fritz A. Henn, Alexander Koppara, Johannes Pantel, Luca Kleineidam, Holger Jahn, Alexander Kurz, Klaus Schmidtke, Friedel M. Reischies, Oliver Peters, Isabella Heuser, Jens Wiltfang, Christian Luckhaus, Michael Wagner, Harald Hampel, Steffen Wolfsgruber, Lutz Frölich, Johannes Schröder, Otto Rienhoff, Frank Jessen, and Hermann-Josef Gertz
Subjects: Male, Oncology, medicine.medical_specialty, psychology [Alzheimer Disease], physiopathology [Cognitive Dysfunction], Prodromal Symptoms, tau Proteins, cerebrospinal fluid [Amyloid beta-Peptides], Logistic regression, physiopathology [Alzheimer Disease], cerebrospinal fluid [Memory Disorders], Alzheimer Disease, Internal medicine, medicine, Humans, physiopathology [Memory Disorders], Memory impairment, Cognitive Dysfunction, In patient, ddc:610, cerebrospinal fluid [Peptide Fragments], Cognitive decline, Psychiatry, Aged, Aged, 80 and over, Memory Disorders, Amyloid beta-Peptides, Middle Aged, amyloid beta-protein (1-42), medicine.disease, Peptide Fragments, cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Cognitive Dysfunction], cerebrospinal fluid [Biomarkers], cerebrospinal fluid [tau Proteins], psychology [Memory Disorders], Csf biomarkers, Biomarker (medicine), Female, Observational study, psychology [Cognitive Dysfunction], Neurology (clinical), Alzheimer's disease, Psychology, Biomarkers
Abstract: Objective: To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD). Methods: We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates. Results: Abnormal CSF β-amyloid 1–42 (Aβ42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF Aβ42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF Aβ42 together with either high CSF tau or CSF phosphorylated tau 181 levels. Conclusions: In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.
Published: 2015
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192. Alzheimer Amyloid Peptide Aβ42 Regulates Gene Expression of Transcription and Growth Factors

Author: Georg Beckmann, Peter St George-Hyslop, Oliver Peters, Lili-Naz Hazrati, Veit Althoff, Murat Eravci, Anette Sommer, Thomas Dyrks, Gerhard Multhaup, John C.S. Breitner, Damian Brockschnieder, Carola G. Schipke, Christian Barucker, Paul E. Fraser, and Anja Harmeier
Subjects: Mice, Transgenic, Peptide, Biology, Real-Time Polymerase Chain Reaction, Hippocampus, DNA-binding protein, Alzheimer Disease, Transcription (biology), Cell Line, Tumor, Gene expression, Animals, Humans, RNA, Messenger, Senile plaques, Protein precursor, Transcription factor, Cerebral Cortex, Psychiatric Status Rating Scales, chemistry.chemical_classification, Regulation of gene expression, Amyloid beta-Peptides, General Neuroscience, General Medicine, Microarray Analysis, Immunohistochemistry, Molecular biology, Peptide Fragments, Psychiatry and Mental health, Clinical Psychology, Insulin-Like Growth Factor Binding Protein 3, Gene Expression Regulation, chemistry, Geriatrics and Gerontology, Insulin-Like Growth Factor Binding Protein 5
Abstract: The pathogenesis of Alzheimer's disease (AD) is characterized by the aggregation of amyloid-{beta} (A{beta}) peptides leading to deposition of senile plaques and a progressive decline of cognitive functions, which currently remains the main criterion for its diagnosis. Robust biomarkers for AD do not yet exist, although changes in the cerebrospinal fluid levels of tau and A{beta} represent promising candidates in addition to brain imaging and genetic risk profiling. Although concentrations of soluble A{beta}42 correlate with symptoms of AD, less is known about the biological activities of A{beta} peptides which are generated from the amyloid-{beta} protein precursor. An unbiased DNA microarray study showed that A{beta}42, at sub-lethal concentrations, specifically increases expression of several genes in neuroblastoma cells, notably the insulin-like growth factor binding proteins 3 and 5 (IGFBP3/5), the transcription regulator inhibitor of DNA binding, and the transcription factor Lim only domain protein 4. Using qRT-PCR, we confirmed that mRNA levels of the identified candidate genes were exclusively increased by the potentially neurotoxic A{beta}42 wild-type peptide, as both the less toxic Aβ40 and a non-toxic substitution peptide A{beta}42 G33A did not affect mRNA levels. In vivo immunohistochemistry revealed a corresponding increase in both hippocampal and cortical IGFBP5 expression in an AD mouse model. Proteomic analyses of human AD cerebrospinal fluid displayed increased in vivo concentrations of IGFBPs. IGFBPs and transcription factors, as identified here, are modulated by soluble A{beta}42 and may represent useful early biomarkers.
Published: 2015
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193. Beyond surgery: clinical and economic impact of Enhanced Recovery After Surgery programs

Author: Tracy Wasylak, Oliver Peters, Nicolas Demartines, Gaëtan-Romain Joliat, and Olle Ljungqvist
Subjects: Program evaluation, medicine.medical_specialty, Debate, 030230 surgery, Health informatics, Perioperative Care, Health administration, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Clinical Protocols, Multidisciplinary approach, Cost Savings, medicine, Humans, Economic impact analysis, Program Development, Enhanced recovery after surgery, Early Ambulation, Enhanced recovery, Perioperative management, business.industry, Health Policy, Nursing research, lcsh:Public aspects of medicine, lcsh:RA1-1270, Surgery, 030220 oncology & carcinogenesis, Implementation, business, Program Evaluation
Abstract: Background Enhanced Recovery After Surgery (ERAS) is a perioperative management based on multimodality and multidisciplinary work. ERAS has been shown to have important clinical and economic benefits, but its spread remains slow worldwide. Discussion This manuscript reviews the overall program benefits and focuses on important aspects for implementation well beyond surgery. Summary Implementation of ERAS pathways improves clinical outcomes and induces substantial economic gains. ERAS is the current surgical revolution.
Published: 2017

194. Technology for home dementia care: A prototype locating system put to the test

Author: Oliver Peters, Natalie Jankowski, Herlind Megges, Brigitte Haas, and Silka Dawn Freiesleben
Subjects: Technology, Applied psychology, Usability, Sample (statistics), Assistive living technologies, Locating systems, 03 medical and health sciences, 0302 clinical medicine, User experience design, Medicine, Dementia, ddc:610, 030212 general & internal medicine, Descriptive statistics, User experience, business.industry, End user, Caregiver burden, Featured Article, medicine.disease, Test (assessment), Psychiatry and Mental health, Caregivers, Neurology (clinical), business, Social psychology, Tracking systems, 030217 neurology & neurosurgery
Abstract: Introduction The user experience of persons with dementia and their primary caregivers with locating systems is not firmly established. Methods Eighteen dyads used a prototype locating system during 4 weeks. Primary outcome measures were ratings of usability, and product functions and features. Secondary outcome measures were caregiver burden, perceived self-efficacy, frequency of use, and willingness to purchase the prototype. Changes in scores between baseline (T1) and end of testing period (T2) were compared by performing independent and dependent samples correlations and descriptive statistics. Results Seventeen dyads made up the final sample. Ratings of usability and product functions and features were fair, but usability ratings were significantly reduced after 4 weeks. Although the prototype was used infrequently by majority of the participants, most caregivers would be willing to purchase the prototype, with men more willing than women. No significant change in technological willingness, caregiver burden, or perceived self-efficacy was found between T1 and T2. Perceived self-efficacy significantly negatively correlated with willingness to purchase the prototype after 4 weeks. Discussion Results highlight the importance of including end users in the research and development phase of locating systems to improve the user experience in home dementia care. Necessary indications for further research are carrying out randomized controlled trials with larger, more representative samples and developing innovative software and hardware solutions., Highlights • A prototype locating system was rated fairly overall but used infrequently. • Usability ratings significantly decreased after 4 weeks of testing. • Willingness to purchase the prototype was high, with men more willing than women. • Perceived self-efficacy negatively correlated with willingness to purchase. • Recommendations to improve user experience are provided.
Published: 2017
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195. Golgin A4 in CSF and granulovacuolar degenerations of patients with Alzheimer disease

Author: Martin Tepel, Joachim Jankowski, Carola G. Schipke, Gary A. Brook, Oliver Peters, Anand Goswami, Eleonora Aronica, Vera Jankowski, Heidi Noels, Joachim Weis, Jasper J. Anink, Stefan Fritz, Felix Kork, Alfred Yamoah, Carmen Huck, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, APH - Aging & Later Life, APH - Mental Health, Pathologie, and RS: CARIM - R3.06 - The vulnerable plaque: makers and markers
Subjects: 0301 basic medicine, Male, pathology [Alzheimer Disease], Mice, 0302 clinical medicine, pathology [Brain], Interquartile range, Medicine, biology, DEMENTIA, diagnosis [Alzheimer Disease], Brain, CEREBROSPINAL-FLUID BIOMARKERS, cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Biomarkers], Immunohistochemistry, Female, pathology [Vacuoles], Antibody, Alzheimer's disease, medicine.drug_class, analysis [Golgi Matrix Proteins], MINI-MENTAL-STATE, Monoclonal antibody, DIAGNOSIS, 03 medical and health sciences, Antigen, Alzheimer Disease, Dementia, Animals, Humans, ddc:610, Aged, metabolism [Vacuoles], Postmortem brain, THERAPEUTIC TARGET, business.industry, Golgi Matrix Proteins, medicine.disease, cerebrospinal fluid [Golgi Matrix Proteins], 030104 developmental biology, metabolism [Brain], Immunology, Vacuoles, biology.protein, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract: ObjectiveTo isolate and identify a new, as yet unknown molecule in CSF that could serve as marker for Alzheimer disease.MethodsWe immunized mice with human CSF and fused hybridomas for monoclonal antibodies and screened these antibodies for their capacity to discriminate CSF of patients with Alzheimer disease from CSF of controls. We then chromatographically isolated the antigen to the best discriminating antibody and identified the antigen using mass spectrometric methods. Thereafter, we quantified the CSF concentration of the antigen in a new cohort of patients with Alzheimer disease and controls and performed immunohistochemistry of postmortem brain tissue derived from patients with Alzheimer disease and controls.ResultsWe generated >200 hybridomas and selected 1 antibody that discriminated CSF from patients with Alzheimer disease from that of controls. We identified golgin A4 as the antigen detected by this antibody. Golgin A4 concentration was significantly higher in CSF from patients with Alzheimer disease than in CSF of controls (145 [interquartile range 125–155] vs 115 [ 99–128] pg/mL, p < 0.001) and demonstrated a substantial discriminative power (area under the receiver operating characteristic curve 0.80, 95% confidence interval 0.67–0.94). Immunohistochemistry of postmortem brain sections from patients with Alzheimer disease revealed a significant accumulation of golgin A4 in granulovacuolar degeneration bodies (GVBs).ConclusionsThese results support the notion that golgin A4 could serve as a diagnostic marker in Alzheimer disease. For validation of this notion, prospective multicenter diagnostic studies will evaluate golgin A4 as diagnostic marker for Alzheimer disease. Furthermore, it has to be determined whether the association of golgin A4 with GVBs is an epiphenomenon or whether golgin A4 plays a more direct role in Alzheimer disease, allowing it to serve as a target in therapeutic treatment strategies.Classification of evidenceThis study provides Class III evidence that elevated CSF golgin A4 levels identify patients with Alzheimer disease.
Published: 2017
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196. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
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197. SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

Author: Wiesje M. van der Flier, Eckart Rüther, Henne Holstege, Johannes Kornhuber, Jens Wiltfang, Charlotte E. Teunissen, Alison Goate, Piotr Lewczuk, Carlos Cruchaga, David Ramonet, Frank Jessen, Markus M. Nöthen, Oliver Peters, Michael T. Heneka, Adam C. Naj, Markus P. Kummer, Christine Herold, Heike Kölsch, R. Heun, Wolfgang Maier, Philip Scheltens, Lutz Frölich, Amy Gerrish, Julius Popp, Vincent Chouraki, Céline Bellenguez, Alzheimer's Disease Neuroimaging Initiative, Dmitriy Drichel, Tim Becker, Lara Buscemi, André Lacour, Monique M.B. Breteler, Stefan Herms, Michael Hüll, Stefanie Heilmann, Alfredo Ramirez, Per Hoffmann, Eva Louwersheimer, Popp, Julius, Neurology, Laboratory Medicine, Human genetics, and NCA - neurodegeneration
Subjects: Apolipoprotein E, Male, cerebrospinal fluid [Apolipoprotein E4], Apolipoprotein E4, cerebrospinal fluid [Nuclear Proteins], genetics [Alzheimer Disease], Genome-wide association study, cerebrospinal fluid [Amyloid beta-Peptides], pathology [Alzheimer Disease], Cerebrospinal fluid, Cognition, Medizinische Fakultät, Genotype, genetics [Amyloid beta-Peptides], genetics [RNA-Binding Proteins], Cognitive decline, Phosphorylation, genetics [Apolipoprotein E4], Genetics (clinical), Genetics, Serine-Arginine Splicing Factors, Association Studies Articles, Nuclear Proteins, RNA-Binding Proteins, genetics [Nuclear Proteins], General Medicine, Single Nucleotide, amyloid beta-protein (1-42), cerebrospinal fluid [Alzheimer Disease], Female, Alzheimer's disease, Signal Transduction, medicine.medical_specialty, RNA-Binding Proteins/cerebrospinal fluid/genetics, Single-nucleotide polymorphism, tau Proteins, Biology, Polymorphism, Single Nucleotide, Alzheimer Disease, ddc:570, Internal medicine, medicine, Dementia, Humans, cerebrospinal fluid [Peptide Fragments], cerebrospinal fluid [RNA-Binding Proteins], ddc:610, Polymorphism, Molecular Biology, Aged, tau Proteins/cerebrospinal fluid/genetics, Amyloid beta-Peptides, Apolipoprotein E4/cerebrospinal fluid/genetics, Nuclear Proteins/cerebrospinal fluid/genetics, medicine.disease, genetics [Peptide Fragments], Peptide Fragments, genetics [tau Proteins], Amyloid beta-Peptides/cerebrospinal fluid/genetics, Endocrinology, cerebrospinal fluid [tau Proteins], Gene Expression Regulation, Alzheimer Disease/cerebrospinal fluid/genetics/pathology, Peptide Fragments/cerebrospinal fluid/genetics, Genome-Wide Association Study
Abstract: Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.
Published: 2017
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198. [O2–10–06]: PROGNOSIS OF CLINICAL PROGRESSION IN SUBJECTIVE COGNITIVE DECLINE USING A CLINICAL DECISION SUPPORT SYSTEM

Author: Frederik Barkhof, Oliver Peters, Jyrki Lötjönen, Rosalinde E.R. Slot, Juha Koikkalainen, Johannes Kornhuber, Frank Jessen, Linda M.P. Wesselman, Wiesje M. van der Flier, Steffen Wolfsgruber, Hilkka Liedes, Betty M. Tijms, Lorena Rami, Nina Coll-Padros, Luca Kleineidam, José Luis Molinuevo, Hanneke F.M. Rhodius-Meester, C.E. Teunissen, Philip Scheltens, and Sietske A.M. Sikkes
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Clinical decision support system, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, Intensive care medicine, business, Clinical progression
Published: 2017
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199. [P2–074]: MODELING OF HIDDEN CAUSES FOR DYNAMIC CHANGES IN STRUCTURAL INTEGRITY AND COGNITION IN SUBJECTIVE COGNITIVE DECLINE: A DELCODE PROJECT

Author: Matthew J. Betts, Frank Jessen, David Berron, Josef Priller, Arturo Cardenas-Blanco, Peter J. Nestor, Michael T. Heneka, Christoph Laske, Oliver Peters, Stefan J. Teipel, Anja Schneider, William D. Penny, Gabriel Ziegler, Michael Wagner, Katharina Buerger, Jens Wiltfang, Annika Spottke, Hartmut Schütze, Klaus Fliessbach, and Emrah Düzel
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Structural integrity, Cognition, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, Psychology, Cognitive psychology, Developmental psychology
Published: 2017
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200. [P4–139]: APPLICATION OF THE ‘A/T/N’ BIOMARKER CLASSIFICATION SYSTEM IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT: CONVERSION RATES TO AD AND OTHER DEMENTIAS

Author: Johannes Kornhuber, Wolfgang Maier, Eckart Rüther, Frank Jessen, Jens Wiltfang, Piotr Lewczuk, Oliver Peters, Michael Wagner, Alexandra Polcher, Lutz Frölich, Michael Hüll, and Steffen Wolfsgruber
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Biomarker (medicine), Medicine, In patient, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment, Neuroscience
Published: 2017
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