Tau mediates the impact of amyloid and vascular disease burden on the trajectory of clinical symptoms.

ABSTRACT:

Introduction

Amyloid (A) and vascular (V) pathologies often co-occur and progress over decades. We leveraged chronicity, defined as the years above a biomarker-positivity threshold, to examine how the timing of A and V relates to cognitive decline.

Methods

We modeled Clinical Dementia Rating-Sum of Boxes (CDR-SB) trajectories in n = 558 participants with [C-11] Pittsburgh compound B positron emission tomography (PET), magnetic resonance imaging-derived white matter hyperintensities (WMHs), and longitudinal CDR assessments. In n = 500 with MK6240 PET, we tested whether tau mediates A-V associations with CDR-SB in a moderated mediation framework.

Results

Whether biomarker "burden" was modeled as chronicity (A+years, V+years), or estimated amyloid and WMH at CDR visits,

SUBMITTER: Du L 

PROVIDER: S-EPMC12572831 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature