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In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease

Meisl, G; Hidari, E; Allinson, K; Rittman, T; DeVos, SL; Sanchez, JS; Xu, CK; ... Klenerman, D; + view all (2021) In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease. Science Advances , 7 (44) , Article eabh1448. 10.1126/sciadv.abh1448. Green open access

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Abstract

Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we can quantify their replication rate in human brains. Notably, we obtain comparable rates in several different datasets, with five different methods of tau quantification, from postmortem seed amplification assays to tau PET studies in living individuals. Our results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the main process controlling the overall rate of accumulation of tau in neocortical regions. The number of seeds doubles only every ∼5 years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD.

Type: Article
Title: In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/sciadv.abh1448
Publisher version: https://doi.org/10.1126/sciadv.abh1448
Language: English
Additional information: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10137920
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