Therriault, J;
Pascoal, TA;
Lussier, FZ;
Tissot, C;
Chamoun, M;
Bezgin, G;
Servaes, S;
... Rosa-Neto, P; + view all
(2022)
Biomarker modeling of Alzheimer’s disease using PET-based Braak staging.
Nature Aging
10.1038/s43587-022-00204-0.
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Abstract
Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [18F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTau) in cerebrospinal fluid (pTau181, pTau217, pTau231 and pTau235) and plasma (pTau181 and pTau231), neurodegeneration and cognitive symptoms. We identified nonlinear AD biomarker trajectories corresponding to the spatial extent of tau-PET, with modest biomarker changes detectable by Braak stage II and significant changes occurring at stages III–IV, followed by plateaus. Early Braak stages were associated with isolated memory impairment, whereas Braak stages V–VI were incompatible with normal cognition. In 159 individuals with follow-up tau-PET, progression beyond stage III took place uniquely in the presence of amyloid-β positivity. Our findings support PET-based Braak staging as a framework to model the natural history of AD and monitor AD severity in living humans.
| Type: | Article |
|---|---|
| Title: | Biomarker modeling of Alzheimer’s disease using PET-based Braak staging |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s43587-022-00204-0 |
| Publisher version: | https://doi.org/10.1038/s43587-022-00204-0 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | 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 > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148259 |
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