Biomarker modeling of Alzheimer's disease using PET-based Braak staging.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 37118445.
- Also identified by DOI 10.1038/s43587-022-00204-0 and PMC identifier 10154209.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Gold-standard diagnosis of Alzheimer's disease (AD) relies on histopathological staging systems. Using the topographical information from [<sup>18</sup>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<sub>181</sub>, pTau<sub>217</sub>, pTau<sub>231</sub> and pTau<sub>235</sub>) and plasma (pTau<sub>181</sub> and pTau<sub>231</sub>), 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.
Medical subject headings
- Alzheimer Disease