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6. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Published
2023
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9. Author Correction: Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., Börjesson-Hanson, Anne, Blackburn, Daniel J., Vijverberg, Everard G. B., De Deyn, Peter Paul, Ducharme, Simon, Jonsson, Michael, Schneider, Anja, Rinne, Juha O., Ludolph, Albert C., Bodenschatz, Ralf, Kordasiewicz, Holly, Swayze, Eric E., Fitzsimmons, Bethany, Mignon, Laurence, Moore, Katrina M., Yun, Chris, Baumann, Tiffany, Li, Dan, Norris, Daniel A., Crean, Rebecca, Graham, Danielle L., Huang, Ellen, Ratti, Elena, Bennett, C. Frank, Junge, Candice, and Lane, Roger M.

Published
2024
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17. Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia

Author

Jansen, Willemijn J, Ossenkoppele, Rik, Tijms, Betty M, Fagan, Anne M, Hansson, Oskar, Klunk, William E, van der Flier, Wiesje M, Villemagne, Victor L, Frisoni, Giovanni B, Fleisher, Adam S, Lleó, Alberto, Mintun, Mark A, Wallin, Anders, Engelborghs, Sebastiaan, Na, Duk L, Chételat, Gäel, Molinuevo, José Luis, Landau, Susan M, Mattsson, Niklas, Kornhuber, Johannes, Sabri, Osama, Rowe, Christopher C, Parnetti, Lucilla, Popp, Julius, Fladby, Tormod, Jagust, William J, Aalten, Pauline, Lee, Dong Young, Vandenberghe, Rik, de Oliveira, Catarina Resende, Kapaki, Elisabeth, Froelich, Lutz, Ivanoiu, Adrian, Gabryelewicz, Tomasz, Verbeek, Marcel M, Sanchez-Juan, Páscual, Hildebrandt, Helmut, Camus, Vincent, Zboch, Marzena, Brooks, David J, Drzezga, Alexander, Rinne, Juha O, Newberg, Andrew, de Mendonça, Alexandre, Sarazin, Marie, Rabinovici, Gil D, Madsen, Karine, Kramberger, Milica G, Nordberg, Agneta, Mok, Vincent, Mroczko, Barbara, Wolk, David A, Meyer, Philipp T, Tsolaki, Magda, Scheltens, Philip, Verhey, Frans RJ, Visser, Pieter Jelle, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Almdahl, Ina S, Arnold, Steven E, Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart NM, Blennow, Kaj, van Buchem, Mark A, Cavedo, Enrica, Chen, Kewei, Chipi, Elena, Cohen, Ann D, Förster, Stefan, Fortea, Juan, Frederiksen, Kristian S, Freund-Levi, Yvonne, Gkatzima, Olymbia, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Johannsen, Peter, Klimkowicz-Mrowiec, Aleksandra, Köhler, Sebastian, Koglin, Norman, van Laere, Koen, de Leon, Mony, Lisetti, Viviana, Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Møllergård, Hanne M, Morris, John C, Nordlund, Arto, Novak, Gerald P, Paraskevas, George P, Perera, Gayan, Peters, Oliver, and Ramakers, Inez HGB

Subjects
Health Services and Systems, Health Sciences, Acquired Cognitive Impairment, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Aging, Dementia, Brain Disorders, Behavioral and Social Science, Neurodegenerative, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Aged, Alzheimer Disease, Amyloid beta-Peptides, Brain, Cognition Disorders, Cognitive Dysfunction, Cross-Sectional Studies, Female, Humans, Male, Memory, Episodic, Mental Status and Dementia Tests, Middle Aged, Positron-Emission Tomography, Reference Values, Amyloid Biomarker Study Group, Other Medical and Health Sciences, Psychology, Cognitive Sciences, Clinical sciences, Clinical and health psychology
Abstract

ImportanceCerebral amyloid-β 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.ObjectiveTo investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.Design, setting, and participantsThis 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 measuresGlobal 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 ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.ResultsAmong 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P

Published
2018

19. Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes

Author

Riviere, Marie‐Emmanuelle, primary, Langbaum, Jessica B., additional, Turner, R. Scott, additional, Rinne, Juha O., additional, Sui, Yihan, additional, Cazorla, Pilar, additional, Ricart, Javier, additional, Meneses, Kathleen, additional, Caputo, Angelika, additional, Tariot, Pierre N., additional, Reiman, Eric M., additional, and Graf, Ana, additional

Published
2023
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20. Association between physical function and neuroimaging measures in a 2‐year multidomain lifestyle randomized controlled trial

Author

Stephen, Ruth, primary, Kulmala, Jenni, additional, Antikainen, Riitta, additional, Kemppainen, Nina, additional, Lehtisalo, Jenni, additional, Mangialasche, Francesca, additional, Ngandu, Tiia, additional, Rinne, Juha O., additional, Soininen, Hilkka, additional, Strandberg, Timo, additional, Kivipelto, Miia, additional, Solomon, Alina, additional, and Hall, Anette, additional

Published
2023
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21. Alzheimer’s disease genetic risk score and neuroimaging biomarkers in the FINGER multidomain lifestyle randomized controlled trial

Author

Hossain, Gazi Saadmaan, primary, Dalmasso, Maria Carolina, additional, Ramirez, Alfredo, additional, Hiltunen, Mikko, additional, Kemppainen, Nina, additional, Lehtisalo, Jenni, additional, Ngandu, Tiia, additional, Rinne, Juha O., additional, Soininen, Hilkka, additional, Stephen, Ruth, additional, Kivipelto, Miia, additional, and Solomon, Alina, additional

Published
2023
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23. Author Correction: Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Author

Mummery, Catherine J., primary, Börjesson-Hanson, Anne, additional, Blackburn, Daniel J., additional, Vijverberg, Everard G. B., additional, De Deyn, Peter Paul, additional, Ducharme, Simon, additional, Jonsson, Michael, additional, Schneider, Anja, additional, Rinne, Juha O., additional, Ludolph, Albert C., additional, Bodenschatz, Ralf, additional, Kordasiewicz, Holly, additional, Swayze, Eric E., additional, Fitzsimmons, Bethany, additional, Mignon, Laurence, additional, Moore, Katrina M., additional, Yun, Chris, additional, Baumann, Tiffany, additional, Li, Dan, additional, Norris, Daniel A., additional, Crean, Rebecca, additional, Graham, Danielle L., additional, Huang, Ellen, additional, Ratti, Elena, additional, Bennett, C. Frank, additional, Junge, Candice, additional, and Lane, Roger M., additional

Published
2023
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24. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight

Author

Heiskanen, Marja A., Honkala, Sanna M., Hentilä, Jaakko, Ojala, Ronja, Lautamäki, Riikka, Koskensalo, Kalle, Lietzén, Martin S., Saunavaara, Virva, Saunavaara, Jani, Helmiö, Mika, Löyttyniemi, Eliisa, Nummenmaa, Lauri, Collado, Maria C., Malm, Tarja, Lahti, Leo, Pietiläinen, Kirsi H., Kaprio, Jaakko, Rinne, Juha O., and Hannukainen, Jarna C.

Published
2021
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25. Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis

Author

Jansen, Willemijn J, Ossenkoppele, Rik, Knol, Dirk L, Tijms, Betty M, Scheltens, Philip, Verhey, Frans RJ, Visser, Pieter Jelle, Aalten, Pauline, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Almdahl, Ina S, Arnold, Steven E, Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart NM, Bibeau, Kristen, Blennow, Kaj, Brooks, David J, van Buchem, Mark A, Camus, Vincent, Cavedo, Enrica, Chen, Kewei, Chetelat, Gael, Cohen, Ann D, Drzezga, Alexander, Engelborghs, Sebastiaan, Fagan, Anne M, Fladby, Tormod, Fleisher, Adam S, van der Flier, Wiesje M, Ford, Lisa, Förster, Stefan, Fortea, Juan, Foskett, Nadia, Frederiksen, Kristian S, Freund-Levi, Yvonne, Frisoni, Giovanni B, Froelich, Lutz, Gabryelewicz, Tomasz, Gill, Kiran Dip, Gkatzima, Olymbia, Gómez-Tortosa, Estrella, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Hildebrandt, Helmut, Ishihara, Lianna, Ivanoiu, Adrian, Jagust, William J, Johannsen, Peter, Kandimalla, Ramesh, Kapaki, Elisabeth, Klimkowicz-Mrowiec, Aleksandra, Klunk, William E, Köhler, Sebastian, Koglin, Norman, Kornhuber, Johannes, Kramberger, Milica G, Van Laere, Koen, Landau, Susan M, Lee, Dong Young, de Leon, Mony, Lisetti, Viviana, Lleó, Alberto, Madsen, Karine, Maier, Wolfgang, Marcusson, Jan, Mattsson, Niklas, de Mendonça, Alexandre, Meulenbroek, Olga, Meyer, Philipp T, Mintun, Mark A, Mok, Vincent, Molinuevo, José Luis, Møllergård, Hanne M, Morris, John C, Mroczko, Barbara, Van der Mussele, Stefan, Na, Duk L, Newberg, Andrew, Nordberg, Agneta, Nordlund, Arto, Novak, Gerald P, Paraskevas, George P, Parnetti, Lucilla, Perera, Gayan, Peters, Oliver, Popp, Julius, Prabhakar, Sudesh, Rabinovici, Gil D, Ramakers, Inez HGB, Rami, Lorena, de Oliveira, Catarina Resende, Rinne, Juha O, Rodrigue, Karen M, and Rodríguez-Rodríguez, Eloy

Subjects
Health Services and Systems, Health Sciences, Clinical Research, Alzheimer's Disease, Vascular Cognitive Impairment/Dementia, Acquired Cognitive Impairment, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cerebrovascular, Neurodegenerative, Prevention, Dementia, Aging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Age Factors, Aged, Aged, 80 and over, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Cerebrospinal Fluid, Cognitive Dysfunction, Female, Genotype, Humans, Male, Middle Aged, Positron-Emission Tomography, Prevalence, Risk Factors, Amyloid Biomarker Study Group, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceCerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.ObjectiveTo use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).Data sourcesRelevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.Study selectionStudies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.Data extraction and synthesisIndividual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.Main outcomes and measuresPrevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.ResultsThe prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.Conclusions and relevanceAmong persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

Published
2015

26. Prevalence of Amyloid PET Positivity in Dementia Syndromes: A Meta-analysis

Author

Ossenkoppele, Rik, Jansen, Willemijn J, Rabinovici, Gil D, Knol, Dirk L, van der Flier, Wiesje M, van Berckel, Bart NM, Scheltens, Philip, Visser, Pieter Jelle, Verfaillie, Sander CJ, Zwan, Marissa D, Adriaanse, Sofie M, Lammertsma, Adriaan A, Barkhof, Frederik, Jagust, William J, Miller, Bruce L, Rosen, Howard J, Landau, Susan M, Villemagne, Victor L, Rowe, Christopher C, Lee, Dong Y, Na, Duk L, Seo, Sang W, Sarazin, Marie, Roe, Catherine M, Sabri, Osama, Barthel, Henryk, Koglin, Norman, Hodges, John, Leyton, Cristian E, Vandenberghe, Rik, van Laere, Koen, Drzezga, Alexander, Forster, Stefan, Grimmer, Timo, Sánchez-Juan, Pascual, Carril, Jose M, Mok, Vincent, Camus, Vincent, Klunk, William E, Cohen, Ann D, Meyer, Philipp T, Hellwig, Sabine, Newberg, Andrew, Frederiksen, Kristian S, Fleisher, Adam S, Mintun, Mark A, Wolk, David A, Nordberg, Agneta, Rinne, Juha O, Chételat, Gaël, Lleo, Alberto, Blesa, Rafael, Fortea, Juan, Madsen, Karine, Rodrigue, Karen M, and Brooks, David J

Subjects
Health Services and Systems, Health Sciences, Genetics, Acquired Cognitive Impairment, Clinical Research, Neurodegenerative, Alzheimer's Disease, Brain Disorders, Aging, Biomedical Imaging, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Adult, Age Factors, Aged, Aged, 80 and over, Amyloid beta-Peptides, Apolipoprotein E4, Brain, Female, Genotype, Humans, Male, Middle Aged, Positron-Emission Tomography, Prevalence, Risk Factors, Amyloid PET Study Group, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceAmyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia.ObjectiveTo use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.Data sourcesThe MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.Study selectionCase reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data.Data extraction and synthesisData were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy).Main outcomes and measuresEstimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.ResultsThe likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P

Published
2015

27. A new perspective for advanced positron emission tomography–based molecular imaging in neurodegenerative proteinopathies

Author

Bottlaender, Michel, Brooks, David, Carroll, Michael A., Chalon, Sylvie, Gee, Anthony, Gerhard, Alexander, Halldin, Christer, Herholz, Karl, Herth, Matthias M., Hinz, Rainer, Knudsen, Gitte M., Kuhnast, Bertrand, López-Picón, Francisco, Moresco, Rosa Maria, Pappata, Sabina, Rinne, Juha O., Rodriguez-Vieitez, Elena, Santiago-Ribeiro, Marie Joao, Turkheimer, Federico E., Van Laere, Koen, Varrone, Andrea, Vercouillie, Johnny, Winkeler, Alexandra, Perani, Daniela, Iaccarino, Leonardo, Lammertsma, Adriaan A., Windhorst, Albert D., Edison, Paul, Boellaard, Ronald, Hansson, Oskar, Nordberg, Agneta, and Jacobs, Andreas H.

Published
2019
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30. Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [11C]SMW139 and [18F]F-DPA.

Author

Alzghool, Obada M., Aarnio, Richard, Helin, Jatta S., Wahlroos, Saara, Keller, Thomas, Matilainen, Markus, Solis, Junel, Danon, Jonathan J., Kassiou, Michael, Snellman, Anniina, Solin, Olof, Rinne, Juha O., and Haaparanta-Solin, Merja

Subjects
POSITRON emission tomography, LABORATORY mice, ANIMAL disease models, IMMUNOSTAINING, AUTORADIOGRAPHY
Abstract

Background: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [11C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [11C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [18F]F-DPA targeting TSPO at the final imaging time point. TG and wild type (WT) mice underwent longitudinal in vivo PET imaging using [11C]SMW139 at 5, 8, 11, and 14 months, followed by [18F]F-DPA PET scan only at 14 months. In vivo imaging results were verified by ex vivo brain autoradiography, immunohistochemical staining, and analysis of [11C]SMW139 unmetabolized fraction in TG and WT mice. Results: Longitudinal change in [11C]SMW139 standardized uptake values (SUVs) showed no statistically significant increase in the neocortex and hippocampus of TG or WT mice, which was consistent with findings from ex vivo brain autoradiography. Significantly higher [18F]F-DPA SUVs were observed in brain regions of TG compared to WT mice. Quantified P2X7-positive staining in the cortex and thalamus of TG mice showed a minor increase in receptor expression with ageing, while TSPO-positive staining in the same regions showed a more robust increase in expression in TG mice as they aged. [11C]SMW139 was rapidly metabolized in mice, with 33% of unmetabolized fraction in plasma and 29% in brain homogenates 30 min after injection. Conclusions: [11C]SMW139, which has a lower affinity for the rodent P2X7 receptor than the human version of the receptor, was unable to image the low expression of P2X7 receptor in the APP/PS1-21 mouse model. Additionally, the rapid metabolism of [11C]SMW139 in mice and the presence of several brain-penetrating radiometabolites significantly impacted the analysis of in vivo PET signal of the tracer. Finally, [18F]F-DPA targeting TSPO was more suitable for imaging reactive glia and neuroinflammatory processes in the APP/PS1-21 mouse model, based on the findings presented in this study and previous studies with this mouse model. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes.

Author

Riviere, Marie‐Emmanuelle, Langbaum, Jessica B., Turner, R. Scott, Rinne, Juha O., Sui, Yihan, Cazorla, Pilar, Ricart, Javier, Meneses, Kathleen, Caputo, Angelika, Tariot, Pierre N., Reiman, Eric M., and Graf, Ana

Abstract

INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE‐1 inhibitor umibecestat in cognitively unimpaired 60‐ to 75‐year‐old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. METHODS: Sixty‐five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 μg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow‐up Aβ positron emission tomography (PET) scans at 18 to 24 months. RESULTS: CAD106 induced measurable serum Aβ immunoglobulin G titers in 41/42 participants, slower rates of Aβ plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: −0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid‐related imaging abnormality cases (one symptomatic). DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of Aβ active immunotherapies in individuals at risk for AD. Highlights: This was the first amyloid‐lowering prevention trial in persons at genetic risk of late‐onset Alzheimer's disease (AD).Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial.CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes.CAD106 was generally safe and well tolerated, with only three amyloid‐related imaging abnormality cases (one symptomatic).Such an approach deserves further evaluation in larger AD prevention trials. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease

Author

Mattsson, Niklas, Groot, Colin, Jansen, Willemijn J., Landau, Susan M., Villemagne, Victor L., Engelborghs, Sebastiaan, Mintun, Mark M., Lleo, Alberto, Molinuevo, José Luis, Jagust, William J., Frisoni, Giovanni B., Ivanoiu, Adrian, Chételat, Gaël, Resende de Oliveira, Catarina, Rodrigue, Karen M., Kornhuber, Johannes, Wallin, Anders, Klimkowicz-Mrowiec, Aleksandra, Kandimalla, Ramesh, Popp, Julius, Aalten, Pauline P., Aarsland, Dag, Alcolea, Daniel, Almdahl, Ina S., Baldeiras, Inês, van Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Cohen, Ann D., Förster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gill, Kiran Dip, Gkatzima, Olymbia, Grimmer, Timo, Hampel, Harald, Herukka, Sanna-Kaisa, Johannsen, Peter, van Laere, Koen, de Leon, Mony J., Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Møllergård, Hanne M., Morris, John C., Mroczko, Barbara, Nordlund, Arto, Prabhakar, Sudesh, Peters, Oliver, Rami, Lorena, Rodríguez-Rodríguez, Eloy, Roe, Catherine M., Rüther, Eckart, Santana, Isabel, Schröder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Verhey, Frans R.J., Vos, Stephanie J.B., van Waalwijk van Doorn, Linda J.C., Waldemar, Gunhild, Wallin, Åsa K., Wiltfang, Jens, Vandenberghe, Rik, Brooks, David J., Fladby, Tormod, Rowe, Christopher C., Drzezga, Alexander, Verbeek, Marcel M., Sarazin, Marie, Wolk, David A., Fleisher, Adam S., Klunk, William E., Na, Duk L., Sánchez-Juan, Pascual, Lee, Dong Young, Nordberg, Agneta, Tsolaki, Magda, Camus, Vincent, Rinne, Juha O., Fagan, Anne M., Zetterberg, Henrik, Blennow, Kaj, Rabinovici, Gil D., Hansson, Oskar, van Berckel, Bart N.M., van der Flier, Wiesje M., Scheltens, Philip, Visser, Pieter Jelle, and Ossenkoppele, Rik

Published
2018
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39. Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment

Author

Herukka, Sanna-Kaisa, Simonsen, Anja Hviid, Andreasen, Niels, Baldeiras, Ines, Bjerke, Maria, Blennow, Kaj, Engelborghs, Sebastiaan, Frisoni, Giovanni B., Gabryelewicz, Tomasz, Galluzzi, Samantha, Handels, Ron, Kramberger, Milica G., Kulczyńska, Agnieszka, Molinuevo, Jose Luis, Mroczko, Barbara, Nordberg, Agneta, Oliveira, Catarina Resende, Otto, Markus, Rinne, Juha O., Rot, Uroš, Saka, Esen, Soininen, Hilkka, Struyfs, Hanne, Suardi, Silvia, Visser, Pieter Jelle, Winblad, Bengt, Zetterberg, Henrik, and Waldemar, Gunhild

Published
2017
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40. Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia

Author

Simonsen, Anja Hviid, Herukka, Sanna-Kaisa, Andreasen, Niels, Baldeiras, Ines, Bjerke, Maria, Blennow, Kaj, Engelborghs, Sebastiaan, Frisoni, Giovanni B., Gabryelewicz, Tomasz, Galluzzi, Samantha, Handels, Ron, Kramberger, Milica G., Kulczyńska, Agnieszka, Molinuevo, Jose Luis, Mroczko, Barbara, Nordberg, Agneta, Oliveira, Catarina Resende, Otto, Markus, Rinne, Juha O., Rot, Uroš, Saka, Esen, Soininen, Hilkka, Struyfs, Hanne, Suardi, Silvia, Visser, Pieter Jelle, Winblad, Bengt, Zetterberg, Henrik, and Waldemar, Gunhild

Published
2017
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49. Additional file 1 of APOE ε4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly

Author

Snellman, Anniina, Ekblad, Laura L., Tuisku, Jouni, Koivumäki, Mikko, Ashton, Nicholas J., Lantero-Rodriguez, Juan, Karikari, Thomas K., Helin, Semi, Bucci, Marco, Löyttyniemi, Eliisa, Parkkola, Riitta, Karrasch, Mira, Schöll, Michael, Zetterberg, Henrik, Blennow, Kaj, and Rinne, Juha O.

Abstract

Additional file 1: eTable 1. Data availability for all variables. eTable 2. Demographics stratified by Aβ positivity. eTable 3. Regional TSPO binding in Aβ+ and Aβ- participants. eFigure 1. Voxel-level differences in 11C-PiB binding between (A) APOE ε4 homozygotes and non-carriers, and (B) APOE ε4 homozygotes and APOE ε4 heterozygotes. eFigure 2. Interaction between Aβ status and APOE ε4 gene dose on regional 11C-PK11195 binding.

Published
2023
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