Association of Plasma p-tau181 and Cognition in Nondemented Subjects Without Aβ42/40 Positivity.

OBJECTIVES

Tau pathology is a hallmark of Alzheimer's disease and contributes to cognitive decline. This study investigated cross-sectional associations between plasma phosphorylated tau at threonine-181 (p-tau181) and cognitive performance in non-demented individuals without Aβ42/40 positivity.

METHODS

Baseline cross-sectional data from 893 participants in the Biomarkers and Cognition Study, Singapore (BIOCIS) were analyzed. Multiple linear regression models, adjusted for age, sex, years of education, Aβ42/40 ratio, APOE ε4 status, and cognitive diagnosis, were conducted.

RESULTS

Higher plasma p-tau181 levels were associated with poorer executive function, slower processing speed, and reduced visuospatial ability. No significant associations were found for global cognition or episodic memory.

CONCLUSIONS

These findings suggest that plasma p-tau181 may serve as a practical biomarker for early cognitive change in Alzheimer's disease. Plasma-based biomarkers may be especially valuable where CSF or PET imaging is less accessible. Longitudinal studies are needed to validate these results.