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Biomarker modeling of Alzheimer's disease using PET-based Braak staging.

Joseph TherriaultTharick Ali PascoalFiroza Z LussierCécile TissotMira ChamounGleb BezginStijn ServaesAndrea L BenedetNicholas James AshtonJonathan M SchottJuan Lantero-RodriguezPeter KunachYi-Ting WangJaime Fernandez-AriasGassan MassarwehPaolo VitaliJean-Paul SoucyParamita Saha-ChaudhuriKaj BlennowHenrik ZetterbergSerge GauthierPedro Rosa-Neto
Published in: Nature aging (2022)
Gold-standard diagnosis of Alzheimer's disease (AD) relies on histopathological staging systems. Using the topographical information from [ 18 F]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 (pTau 181 , pTau 217 , pTau 231 and pTau 235 ) and plasma (pTau 181 and pTau 231 ), 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.
Keyphrases
  • pet ct
  • positron emission tomography
  • cerebrospinal fluid
  • computed tomography
  • pet imaging
  • lymph node
  • depressive symptoms
  • working memory
  • healthcare
  • physical activity
  • mild cognitive impairment
  • social media