9 results on '"Genthon, R."'
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2. Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease
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Penner, G, Lecocq, S, Chopin, A, Vedoya, X, Lista, S, Vergallo, A, Cavedo, E, Lejeune, F, Dubois, B, Hampel, H, Bakardjian, H, Benali, H, Bertin, H, Bonheur, J, Boukadida, L, Boukerrou, N, Chiesa, Pa, Colliot, O, Dubois, M, Epelbaum, S, Gagliardi, G, Genthon, R, Habert, M, Houot, M, Kas, A, Lamari, F, Levy, M, Metzinger, C, Mochel, F, Nyasse, F, Poisson, C, Potier, M, Revillon, M, Santos, A, Andrade, Ks, Sole, M, Surtee, M, de Schotten, Mt, Younsi, N, Afshar, M, Aguilar, Lf, Akman-Anderson, L, Aremas, J, Avila, J, Babiloni, C, Baldacci, F, Batrla, R, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Cacciola, F, Caraci, F, Caruso, G, Castrillo, J, Ceravolo, R, Corbo, M, Corvol, J, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Emanuele, E, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Geerts, H, Giacobini, E, Giorgi, Fs, Goetzl, Ej, Graziani, M, Haberkamp, M, Hanisch, B, Herholz, K, Hernandez, F, Imbimbo, Bp, Kapogiannis, D, Karran, E, Kiddle, Sj, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehericy, S, Lemercier, P, Llavero, F, Lorenceau, J, Lucia, A, Mango, D, Mapstone, M, Neri, C, Nistico, R, O'Bryant, Se, Palermo, G, Perry, G, Ritchie, C, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Valenzuela, Pl, Vellas, B, Verdooner, Sr, Villain, N, Giudici, Kv, Watling, M, Welikovitch, La, Woodcock, J, Younesi, E, Zugaza, Jl, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-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), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gasset, Maria
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Male ,Aging ,Amyloid β ,MESH: SELEX Aptamer Technique ,[SDV]Life Sciences [q-bio] ,Oligonucleotides ,Artificial Gene Amplification and Extension ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Pathology and Laboratory Medicine ,Biochemistry ,Polymerase Chain Reaction ,Diagnostic Radiology ,Negative selection ,Medical Conditions ,Mathematical and Statistical Techniques ,0302 clinical medicine ,MESH: Aged, 80 and over ,MESH: Early Diagnosis ,80 and over ,Medicine and Health Sciences ,Biomarker discovery ,Tomography ,Aged, 80 and over ,MESH: Aged ,screening and diagnosis ,0303 health sciences ,Multidisciplinary ,Nucleotides ,Mathematical Models ,Radiology and Imaging ,SELEX Aptamer Technique ,Settore MED/37 - Neuroradiologia ,Neurodegenerative Diseases ,MESH: Case-Control Studies ,MESH: Amyloid beta-Peptides ,Detection ,Neurology ,Neurological ,Medicine ,Biomedical Imaging ,Female ,Biotechnology ,4.2 Evaluation of markers and technologies ,Research Article ,Amyloid ,General Science & Technology ,Imaging Techniques ,Science ,Aptamer ,Neuroimaging ,and over ,Computational biology ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Clinical Research ,Diagnostic Medicine ,Alzheimer Disease ,Mental Health and Psychiatry ,Acquired Cognitive Impairment ,Humans ,Risk factor ,Molecular Biology Techniques ,Molecular Biology ,Aged ,030304 developmental biology ,Amyloid beta-Peptides ,MESH: Humans ,Prevention ,Neurosciences ,Alzheimer Precision Medicine Initiative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Biology and Life Sciences ,Omics ,MESH: Male ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Early Diagnosis ,Case-Control Studies ,MESH: Biomarkers ,Dementia ,INSIGHT-preAD study group ,MESH: Female ,Biomarkers ,Positron Emission Tomography ,030217 neurology & neurosurgery ,MESH: Alzheimer Disease ,Neuroscience - Abstract
International audience; The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer's disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
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- 2021
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3. Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease
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Chiesa P. A., Cavedo E., Vergallo A., Lista S., Potier M. -C., Habert M. -O., Dubois B., Thiebaut de Schotten M., Hampel H., Audrain C., Auffret A., Bakardjian H., Baldacci F., Batrancourt B., Benakki I., Benali H., Bertin H., Bertrand A., Boukadida L., Cacciamani F., Causse V., Cherif Touil S., Colliot O., Dalla Barba G., Depaulis M., Dos Santos A., Dubois M., Epelbaum S., Fontaine B., Francisque H., Gagliardi G., Genin A., Genthon R., Glasman P., Gombert F., Habert M. O., Hewa H., Houot M., Jungalee N., Kas A., Kilani M., La Corte V., Le Roy F., Lehericy S., Letondor C., Levy M., Lowrey M., Ly J., Makiese O., Masetti I., Mendes A., Metzinger C., Michon A., Mochel F., Nait Arab R., Nyasse F., Perrin C., Poirier F., Poisson C., Potier M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Uspenskaya O., Vlaincu M., Aguilar L. F., Babiloni C., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Corvol J. -C., Claudio Cuello A., Cummings J. L., Depypere H., Duggento A., Durrleman S., Escott-Price V., Federoff H., Teresa Ferretti M., Fiandaca M., Frank R. A., Garaci F., Geerts H., George N., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lorenceau J., Mango D., Mapstone M., Neri C., Nistico R., O'Bryant S. E., Palermo G., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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), Treat SVD, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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), Université de Bordeaux (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Maladies Cognitives et Comportementales [Paris], Fraunhofer Center for Assistive Information and Communication Solutions [Porto] (Fraunhofer AICOS), Fraunhofer (Fraunhofer-Gesellschaft), Ariana Pharmaceuticals, McGill University = Université McGill [Montréal, Canada], Universidad Autonoma de Madrid (UAM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Pisa - Università di Pisa, Federal Institute of Drugs and Medical Devices [Bonn], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universita degli Studi di Messina, University of Catania [Italy], University of Cambridge [UK] (CAM), Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Università degli Studi di Roma Tor Vergata [Roma], University of Pavia, Cardiff University, Universität Zürich [Zürich] = University of Zurich (UZH), University of California [Irvine] (UCI), University of California, Siemens Healthineers, Digital Services, Digital Technology and Innovation, In Silico Biosciences (ISB), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of California [San Francisco] (UCSF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Manchester [Manchester], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Abbvie Inc. [North Chicago], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Britsh Columbia [Vancouver], Cedars-Sinai Medical Center, Functional Neuromodulation, CIBER de Enfermedades Raras (CIBERER), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute [Rome, Italy] (EBRI), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), University of North Texas Health Science Center [Fort Worth], University of Auckland [Auckland], University of Edinburgh, Università degli Studi di Siena = University of Siena (UNISI), Harvard Medical School [Boston] (HMS), Keck School of Medicine [Los Angeles], University of Southern California (USC), Indiana State University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), NeuroVision Imaging, Fondation pour la Recherche sur Alzheimer, Center for Drug Evaluation and Research (CDER), European Society for Translational Medicine (EUSTM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fraunhofer AICOS [Porto], McGill University, Sapienza University [Rome], University of Zürich [Zürich] (UZH), Università degli Studi di Roma 'La Sapienza' [Rome], CHU Pitié-Salpêtrière [APHP], Service de neuro-radiologie [CHU Pitié-Salpêtrière], Università degli Studi di Siena (UNISI), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Sorbonne Université (SU)-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Universidad Autónoma de Madrid (UAM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Sans affiliation, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Pavia = University of Pavia (UNIPV), University of California [Irvine] (UC Irvine), University of California (UC), University of California [San Francisco] (UC San Francisco), University of British Columbia [Vancouver], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M. -C., Habert, M. -O., Dubois, B., Thiebaut de Schotten, M., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Castrillo, J., Ceravolo, R., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Apolipoprotein E ,Epidemiology ,Brain activity and meditation ,Precuneus ,Disease ,Neuropsychological Tests ,Hippocampus ,Cohort Studies ,[SCCO]Cognitive science ,0302 clinical medicine ,Medicine ,Longitudinal Studies ,Default mode network ,ComputingMilieux_MISCELLANEOUS ,Brain Mapping ,Subjective memory complaints ,Brain functional dynamic ,Health Policy ,Precision medicine ,fMRI ,Settore BIO/14 ,Brain ,Brain functional dynamics ,Alzheimer's disease ,Magnetic Resonance Imaging ,Temporal Lobe ,Frontal Lobe ,Psychiatry and Mental health ,medicine.anatomical_structure ,Cohort ,Biomarker (medicine) ,Female ,Amyloid ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Apolipoproteins E ,Developmental Neuroscience ,Alzheimer Disease ,Humans ,Aged ,Resting state fMRI ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,030104 developmental biology ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
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- 2019
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4. Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study
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Baldacci, F., Lista, S., Manca, M. L., Chiesa, P. A., Cavedo, E., Lemercier, P., Zetterberg, H., Blennow, K., Habert, M. -O., Potier, M. C., Dubois, B., Vergallo, A., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Houot, M., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. -C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., de Schotten, M. T., Younsi, N., Afshar, M., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Caruso, G., Castrillo, J., Ceravolo, R., Corbo, M., Corvol, J. -C., Claudio, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., Zugaza, J. L., 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), University of Pisa - Università di Pisa, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Sahlgrenska Academy at University of Gothenburg [Göteborg], University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-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)
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Male ,BIOMARKER ,0301 basic medicine ,Oncology ,Aging ,Neurology ,[SDV]Life Sciences [q-bio] ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Medical and Health Sciences ,lcsh:RC346-429 ,MESH: Cognitive Dysfunction ,Alzheimer’s disease ,Biomarkers ,Mild cognitive impairment ,Neurofilament light chain ,Subjective memory complainers ,Tau ,0302 clinical medicine ,Neurofilament Proteins ,Medicine and Health Sciences ,BRAIN ,MESH: Neurofilament Proteins ,RISK ,Settore FIS/07 ,NEURODEGENERATION ,Cognition ,ASSOCIATION ,MESH: Follow-Up Studies ,Alzheimer's disease ,MESH: Amyloid beta-Peptides ,MESH: tau Proteins ,ALZHEIMERS-DISEASE ,POSITIVITY ,Neurological ,Cohort ,Biomarker (medicine) ,Female ,medicine.medical_specialty ,Cognitive Neuroscience ,tau Proteins ,Subjective ,Affect (psychology) ,VALIDATION ,lcsh:RC321-571 ,subjective memory complainers ,mild cognitive impairment ,biomarkers ,s disease ,03 medical and health sciences ,memory complainers ,Clinical Research ,Alzheimer Disease ,Internal medicine ,NEUROFILAMENT LIGHT-CHAIN ,Acquired Cognitive Impairment ,medicine ,Humans ,Cognitive Dysfunction ,Vitamin B12 ,Allele ,Alzheimer’ ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,lcsh:Neurology. Diseases of the nervous system ,Amyloid beta-Peptides ,MESH: Humans ,business.industry ,Research ,Prevention ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer Precision Medicine Initiative ,COGNITIVE IMPAIRMENT ,MESH: Male ,Brain Disorders ,030104 developmental biology ,MESH: Biomarkers ,Dementia ,Neurology (clinical) ,business ,INSIGHT-preAD study group ,MESH: Female ,MESH: Alzheimer Disease ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
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- 2020
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5. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
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Vergallo, A, Bun, R, Toschi, N, Baldacci, F, Zetterberg, H, Blennow, K, Cavedo, E, Lamari, F, Habert, M, Dubois, B, Floris, R, Garaci, F, Lista, S, Hampel, H, Audrain, C, Auffret, A, Bakardjian, H, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cherif Touil, S, Chiesa, Pa, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, Mo, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, Mc, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, Mc, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Aguilar, Lf, Babiloni, C, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Coman, Cm, Corvol, Jc, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehéricy, S, Lorenceau, J, Mapstone, M, Neri, C, Nisticò, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rossi, S, Santarnecchi, E, Schneider, Ls, Sporns, O, Verdooner, Sr, Villain, N, Welikovitch, L, Woodcock, J, Younesi, E, Vergallo, A., Bun, R. -S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M. -O., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Bun, R. S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C. M., Corvol, J. C., Cuello, A. C., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lorenceau, J., Mapstone, M., Neri, C., Nistico, R., Nyasse-Messene, F., O'Bryant, S. E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L. S., Sporns, O., Verdooner, S. R., Villain, N., Welikovitch, L., Woodcock, J., and Younesi, E.
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0301 basic medicine ,Epidemiology ,Alzheimer's disease ,Amyloid PET ,Cerebrospinal fluid ,Monocentric ,Preclinical ,Subjective memory complainers ,SUVR ,Synergistic ,Tau protein ,α-Synuclein ,chemistry.chemical_compound ,0302 clinical medicine ,biology ,Health Policy ,Settore FIS/07 ,Settore BIO/14 ,Pathophysiology ,Psychiatry and Mental health ,medicine.symptom ,medicine.medical_specialty ,Amyloid ,Asymptomatic ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychiatry and Mental Health ,Internal medicine ,mental disorders ,medicine ,Dementia ,Alpha-synuclein ,business.industry ,Alzheimer's disease biomarkers ,medicine.disease ,030104 developmental biology ,Endocrinology ,nervous system ,chemistry ,Subjective memory complainer ,biology.protein ,business ,030217 neurology & neurosurgery - Abstract
Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
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- 2018
6. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD
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Vergallo, A., Houot, M., Cavedo, E., Lemercier, P., Vanmechelen, E., De Vos, A., Habert, M. -O., Potier, M. -C., Dubois, B., Lista, S., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M. O., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Younsi, N., Afshar, M., Flores Aguilar, L., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Castrillo, J., Ceravolo, R., Chiesa, P. A., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Marie-Odile, H., Herholz, K., Hernandez, F., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lucia, A., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de médecine nucléaire [CHU Pitié-Salpétrière]
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Male ,0301 basic medicine ,Apolipoprotein E ,Epidemiology ,[SDV]Life Sciences [q-bio] ,PROGRESSION ,Disease ,Cognition ,0302 clinical medicine ,Amyloid precursor protein ,Medicine and Health Sciences ,Aspartic Acid Endopeptidases ,medicine.diagnostic_test ,biology ,Health Policy ,Settore BIO/14 ,Brain ,Alzheimer's disease ,Healthy Volunteers ,3. Good health ,GENOTYPE ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,Positron emission tomography ,Cohort ,Biomarker (medicine) ,Female ,EXPRESSION ,medicine.medical_specialty ,BIOMARKERS ,Standardized uptake value ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Sexual dimorphism ,Apolipoproteins E ,Sex Factors ,Developmental Neuroscience ,Alzheimer Disease ,Internal medicine ,mental disorders ,medicine ,Humans ,BACE1 biomarkers ,Aged ,Plasma BACE1 ,DECLINE ,Amyloid beta-Peptides ,business.industry ,030104 developmental biology ,Endocrinology ,Positron-Emission Tomography ,Disease modifying ,biology.protein ,Neurology (clinical) ,Amyloid Precursor Protein Secretases ,Geriatrics and Gerontology ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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- 2019
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7. Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease
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Cacciamani, Federica, Tandetnik, Caroline, Gagliardi, Geoffroy, Bertin, Hugo, Habert, Marie-Odile, Hampel, Harald, Boukadida, Laurie, Révillon, Marie, Epelbaum, Stéphane, Dubois, Bruno, Audrain, C, Auffret, A, Bakardjian, H, Baldacci, F, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cavedo, E, Cherif Touil, S, Chiesa, P A, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, B, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, M O, Hampel, H, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lista, S, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, M C, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, M C, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Institut de Mécanique et d'Ingénierie de Bordeaux (I2M), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-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)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuroradiologie [CHU Pitié-Salpêtrière], École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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 [APHP], HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), 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 [APHP]-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 [APHP]-Inria de Paris, Cacciamani, Federica, Tandetnik, Caroline, Gagliardi, Geoffroy, Bertin, Hugo, Habert, Marie-Odile, Hampel, Harald, Boukadida, Laurie, Révillon, Marie, Epelbaum, Stéphane, Dubois, Bruno, Audrain, C, Auffret, A, Bakardjian, H, Baldacci, F, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cavedo, E, Cherif Touil, S, Chiesa, P A, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, B, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, M O, Hampel, H, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lista, S, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, M C, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, M C, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris
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Male ,Ethylene Glycol ,[SDV]Life Sciences [q-bio] ,awarene ,Neuropsychological Tests ,Alzheimer’s disease ,awareness ,biomarkers ,cognitive complaints ,subjective cognitive decline ,Aged ,Aged, 80 and over ,Alzheimer Disease ,Analysis of Variance ,Aniline Compounds ,Brain ,Brain Mapping ,Cognitive Dysfunction ,Ethylene Glycols ,Female ,Functional Laterality ,Humans ,Positron-Emission Tomography ,Psychiatric Status Rating Scales ,Surveys and Questionnaires ,Awareness ,cognitive complaint ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,80 and over ,Surveys and Questionnaire ,Aniline Compound ,Psychiatric Status Rating Scale ,Alzheimer's disease ,Clinical Psychology ,Psychiatry and Mental Health ,biomarker ,Neuropsychological Test ,Geriatrics and Gerontology ,Human - Abstract
International audience; Background:Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer’s disease (AD). Objective:In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Methods:Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Results:Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the “low awareness” group showed greater amyloid burden and lower cortical metabolism, compared to the “high awareness” group. Conclusion:This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.
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- 2017
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8. Basal Forebrain Volume, but Not Hippocampal Volume, Is a Predictor of Global Cognitive Decline in Patients With Alzheimer's Disease Treated With Cholinesterase Inhibitors
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Teipel, Sj, Cavedo, E, Hampel, H, Grothe, Mj, Aguilar, Lf, Babiloni, C, Baldacci, F, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Chiesa, Pa, Colliot, O, Coman, C, Corvol, J, Cuello, Ac, Depypere, H, Dubois, B, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Genthon, R, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Habert, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Lamari, F, Langevin, T, Lehericy, S, Lista, S, Lorenceau, J, Mapstone, M, Neri, C, Nistico, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rojkova, K, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Verdooner, Sr, Vergallo, A, Villain, N, Welikovitch, La, Woodcock, J, Younesi, E, and Cummings, Jl
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Aging ,hippocampus ,Hippocampus ,Neurodegenerative ,Alzheimer's Disease ,lcsh:RC346-429 ,cholinergic treatment ,memory ,0302 clinical medicine ,Medicine and Health Sciences ,Psychology ,Medicine ,Cognitive decline ,Episodic memory ,basal forebrain ,Original Research ,Basal forebrain ,Settore FIS/07 ,05 social sciences ,Cognition ,IMPAIRMENT ,Manchester Institute for Collaborative Research on Ageing ,Neurology ,Neurological ,Cohort ,DONEPEZIL ,Cardiology ,NUCLEUS BASALIS ,ADAS-COG ,MRI ,CHOLINERGIC SYSTEM ,medicine.medical_specialty ,ResearchInstitutes_Networks_Beacons/MICRA ,Clinical Sciences ,COMPOSITE SCORE ,ATROPHY ,050105 experimental psychology ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Behavioral and Social Science ,Acquired Cognitive Impairment ,Dementia ,0501 psychology and cognitive sciences ,ddc:610 ,lcsh:Neurology. Diseases of the nervous system ,business.industry ,Alzheimer's Disease Neuroimaging Initiative ,Neurosciences ,Alzheimer Precision Medicine Initiative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,prediction ,medicine.disease ,NEUROIMAGING INITIATIVE ADNI ,Brain Disorders ,SUBSTANTIA INNOMINATA ,executive function ,Cholinergic treatment ,Executive function ,Memory ,Prediction ,Cholinergic ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background: Predicting the progression of cognitive decline in Alzheimer's disease (AD) is important for treatment selection and patient counseling. Structural MRI markers such as hippocampus or basal forebrain volumes might represent useful instruments for the prediction of cognitive decline. The primary objective was to determine the predictive value of hippocampus and basal forebrain volumes for global and domain specific cognitive decline in AD dementia during cholinergic treatment.Methods: We used MRI and cognitive data from 124 patients with the clinical diagnosis of AD dementia, derived from the ADNI-1 cohort, who were on standard of care cholinesterase inhibitor treatment during a follow-up period between 0.4 and 3.1 years. We used linear mixed effects models with cognitive function as outcome to assess the main effects as well as two-way interactions between baseline volumes and time controlling for age, sex, and total intracranial volume. This model accounts for individual variation in follow-up times.Results: Basal forebrain volume, but not hippocampus volume, was a significant predictor of rates of global cognitive decline. Larger volumes were associated with smaller rates of cognitive decline. Left hippocampus volume had a modest association with rates of episodic memory decline. Baseline performance in global cognition and memory was significantly associated with hippocampus and basal forebrain volumes; in addition, basal forebrain volume was associated with baseline performance in executive function.Conclusions: Our findings indicate that in AD dementia patients, basal forebrain volume may be a useful marker to predict subsequent cognitive decline during cholinergic treatment.
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- 2018
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9. Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults
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ten Kate, Mara, Visser, Pieter Jelle, Bakardjian, Hovagim, Barkhof, Frederik, Sikkes, Sietske A. M., van der Flier, Wiesje M., Scheltens, Philip, Hampel, Harald, Habert, Marie-Odile, Dubois, Bruno, Tijms, Betty M., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, B., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hampel, H., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-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), AXA Research Fund, Sorbonne Université (SU), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Neurology, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
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0301 basic medicine ,PRECLINICAL ALZHEIMERS-DISEASE ,Aging ,0302 clinical medicine ,Original Research ,biology ,medicine.diagnostic_test ,subjective memory complaints ,APOE GENOTYPE ,Alzheimer's disease ,medicine.anatomical_structure ,Cerebral cortex ,Positron emission tomography ,Cardiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,STRUCTURAL COVARIANCE ,Alzheimer’s disease ,MRI ,medicine.medical_specialty ,Amyloid ,Amyloid beta ,Cognitive Neuroscience ,graph theory ,PLAQUE BURDEN ,Standardized uptake value ,Cognitive neuroscience ,SPATIAL-PATTERNS ,gray matter network ,lcsh:RC321-571 ,Graph theory ,Gray matter network ,PET ,Subjective memory complaints ,03 medical and health sciences ,POSITRON-EMISSION-TOMOGRAPHY ,Internal medicine ,CEREBRAL-CORTEX ,medicine ,Dementia ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Pathological ,business.industry ,HUMAN CORTICAL NETWORKS ,medicine.disease ,amyloid beta ,BRAIN NETWORKS ,030104 developmental biology ,PROSPECTIVE COHORT ,biology.protein ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
for the INSIGHT-preAD study group; International audience; The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [ 18 F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (β = −0.12, p < 0.05), and small world values (β = −0.16, p < 0.01). Associations were most prominent in orbito-and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.
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- 2018
- Full Text
- View/download PDF
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