Year: 2020
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Amyloid beta (Aβ) deposition was identified to precede tau pathology and neurodegeneration in familial Alzheimer's disease (AD). But the divergence between sporadic and familial AD limits the extension of these findings to sporadic AD. METHODS: Longitudinal changes of biomarkers among different stages were assessed using linear mixed-effects models. The slopes of the models were used to estimate rates of change to calculate the biomarker trajectories in sporadic AD. RESULTS: Cerebrospinal fluid (CSF) Aβ was estimated to decline 45.2 years (abnormal: 27.8 years) before dementia, and Aβ deposition seemed to increase 31.7 years (abnormal: 26.7 years) before dementia. It was estimated to take 29.0 years (CSF t-tau), 12.2 years (memory), 11.6 years (hippocampus), 9.3 years (hypometabolism), and 6.1 years (cognition) to move from normal to dementia. DISCUSSION: The trajectory in sporadic AD is led by Aβ accumulation, followed by CSF t-tau increase, memory deficits, brain atrophy, hypometabolism, and cognitive decline.
DOI: 10.1002/dad2.12095
Institutions: Qingdao University, Qingdao Municipal Hospital, Shanghai Medical College of Fudan University, Fudan University, Huashan Hospital, Affiliated Hospital of Qingdao University, University of Cambridge, Cambridgeshire and Peterborough NHS Foundation Trust, Wellcome Trust, Medical Research Council, Army Medical University, Daping Hospital, National University of Singapore, Harvard University, Massachusetts General Hospital, Université de Montpellier, Centre Hospitalier Universitaire de Montpellier, McGill University Research Centre for Studies in Aging, McGill University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, TauRx Pharmaceuticals, National Natural Science Foundation of China, Fudan University, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging
Awards: G1012222616, G1298807586, Genetic Epidemiology of Alzheimer's Disease in African Americans, G1554142629, G1593117279, G1650819308, White Matter Hyperintentisities in Aging and Dementia, G1880935189, G2100670906, Epidemiology of Biomarkers of Risk and Progression in LOAD, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2522063444, Epidemiology of Dementia In An Urban Community, G2835601961, G29951154, G3131374986, G3216574877, G3553156159, Tau PET imaging in racially/ethnically diverse middle-aged adults, G3710456697, G3752451908, G3783051889, G3870774570, G3908963977, G3939930721, G3966393351, G4119534169, G43180419, G4475667458, G4501223628, G470063782, G4800177743, G5207404921, G5209990037, G528601746, G5324093878, G5365730499, G5574148142, Genetic Epidemiology of Cerebrovascular Factors in Alzheimer's Disease, G5654639750, G5740349702, Resilience Mechanisms Underlying Racial/Ethnic Disparities in Alzheimer’s Disease, White matter hyperintensities in Aging and Dementia, G5850682332, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6929861, G6948409098, Offpsring Study of Mechanisms for Racial Disparities in Alzheimer's Disease, G72415811, G7298697282, G764699806, G7799614282, G781725486, G8151151163, G8228018387, G8281378126, G839208290, G8852128998, G8895907669, G8897063270, G8899475930, G8957659042
OpenAlex ID: W3048865760