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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
Nature aging, 06/2022, Volume: 2, Issue: 6Journal Article
Gold-standard diagnosis of Alzheimer's disease (AD) relies on histopathological staging systems. Using the topographical information from FMK6240 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 (pTau , pTau , pTau and pTau ) and plasma (pTau and pTau ), 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.
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