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Four distinct trajectories of tau deposition identified in Alzheimer's disease

Authors
 Jacob W Vogel  ;  Alexandra L Young  ;  Neil P Oxtoby  ;  Ruben Smith  ;  Rik Ossenkoppele  ;  Olof T Strandberg  ;  Renaud La Joie  ;  Leon M Aksman  ;  Michel J Grothe  ;  Yasser Iturria-Medina  ;  Alzheimer’s Disease Neuroimaging Initiative  ;  Michael J Pontecorvo  ;  Michael D Devous  ;  Gil D Rabinovici  ;  Daniel C Alexander  ;  Chul Hyoung Lyoo  ;  Alan C Evans  ;  Oskar Hansson 
Citation
 NATURE MEDICINE, Vol.27(5) : 871-881, 2021-05 
Journal Title
NATURE MEDICINE
ISSN
 1078-8956 
Issue Date
2021-05
MeSH
Aged ; Alzheimer Disease / classification ; Alzheimer Disease / pathology* ; Carbolines / pharmacology ; Cerebral Cortex / diagnostic imaging ; Cerebral Cortex / pathology* ; Cognitive Dysfunction / pathology* ; Female ; Humans ; Male ; Neuroimaging / methods ; Phenotype ; Positron-Emission Tomography / methods ; Radiopharmaceuticals / administration & dosage ; Spatio-Temporal Analysis ; tau Proteins / metabolism*
Abstract
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.
Full Text
https://www.nature.com/articles/s41591-021-01309-6
DOI
10.1038/s41591-021-01309-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184819
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