Nature aging · 2022
Biomarker modeling of Alzheimer's disease using PET-based Braak staging.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Therriault Joseph, Pascoal Tharick A, Lussier Firoza Z, Tissot Cécile, Chamoun Mira, Bezgin Gleb, Servaes Stijn, Benedet Andrea L, Ashton Nicholas J, Karikari Thomas K, Lantero-Rodriguez Juan, Kunach Peter, Wang Yi-Ting, Fernandez-Arias Jaime, Massarweh Gassan, Vitali Paolo, Soucy Jean-Paul, Saha-Chaudhuri Paramita, Blennow Kaj, Zetterberg Henrik, Gauthier Serge, Rosa-Neto Pedro
Аннотация
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.