Tau profiling across Alzheimer's disease staging reveals vulnerability to disease pathophysiology.

ABSTRACT:

Background

Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.

Methods

To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.

Results

Longitudinal and cross-sectional MCA in large aging cohort identified individual profiles (N = 753) expressing tau load in the entorhinal, limbic and neocortical regions. Using these profiles, we found neuropsychological and blood-based milestones of early and late disease stages. Finally, we also found evidence of rapid tau load increases and cognitive decline centered at the early-to-mid neocortical stages of Alzheimer's disease.

Conclusions

Stage system based on tau

SUBMITTER: Bezgin G 

PROVIDER: S-EPMC12397142 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature