期刊
NATURE MEDICINE
卷 27, 期 5, 页码 871-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01309-6
关键词
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资金
- government of Canada through a tri-council Vanier Canada Graduate Doctoral fellowship from the McGill Centre for Integrative Neuroscience and the Healthy Brains, Healthy Lives initiative
- National Institutes of Health (NIH) [T32MH019112]
- Medical Research Council Skills Development Fellowship [MR/T027800/1]
- UK Research and Innovation Future Leaders Fellow [MR/S03546X/1]
- UK National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Engineering and Physical Sciences Research Council [EP/M020533/1]
- Miguel Servet program [CP19/00031]
- Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional [PI20/00613]
- NIH [K99AG065501]
- European Union's Horizon 2020 research and innovation programme [666992]
- Swedish Research Council [2016-00906]
- Knut and Alice Wallenberg Foundation [2017-0383]
- Marianne and Marcus Wallenberg Foundation [2015.0125]
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Alzheimer's Foundation [AF-939932]
- Swedish Brain Foundation [FO2019-0326]
- Swedish Parkinson Foundation [1280/20]
- Skane University Hospital Foundation [2020-O000028]
- Regionalt Forskningsstod [2020-0314]
- Swedish Federal Government under the ALF agreement [2018-Projekt0279]
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [NRF2018R1D1A1B07049386, NRF2020R1F1A1076154]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Ministry of Health and Welfare, Republic of Korea [HI18C1159]
- National Institute on Aging (NIA) [R01 AG045611, P50 AG23501, P01 AG019724]
- GE Healthcare
- ADNI (NIH) [U01 AG024904]
- Department of Defense ADNI [W81XWH-12-2-0012]
- NIA
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Bioclinica
- Biogen
- Bristol Myers Squibb
- CereSpir
- Cogstate
- Eisai
- Elan Pharmaceuticals
- Eli Lilly and Company
- EUROIMMUN
- F. Hoffmann-La Roche
- Genentech
- Fujirebio
- IXICO
- Janssen Alzheimer Immunotherapy Research Development
- Johnson & Johnson Pharmaceutical Research Development
- Lumosity
- Lundbeck
- Merck
- Meso Scale Diagnostics
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- MRC [UKDRI-1001] Funding Source: UKRI
By using an unbiased subtyping algorithm, the study systematically characterized longitudinal tau variability in human Alzheimer's disease, identifying four trajectories of tau deposition with distinct clinical features. The results suggest that variation in tau pathology is common and systematic, potentially necessitating a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.
Systematic characterization of longitudinal tau variability in human Alzheimer's disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features. Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.
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