Sex differences in vulnerability to tau pathology: Impact on cognitive decline

Zeighami, Y., Tremblay, C. et Dadar, M. (2025). Sex differences in vulnerability to tau pathology: Impact on cognitive decline. Alzheimer's and Dementia, 21 (10). Article e70634. ISSN 1552-5260 1552-5279 DOI 10.1002/alz.70634

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Résumé

Abstract

INTRODUCTION:
Although the link between the presence of amyloid and tau pathologies, neurodegeneration, and cognitive decline in aging individuals is established, it is less clear whether there are sex differences in vulnerability to these pathologies.

METHODS:
A total of 1464 participants (7168 longitudinal assessments, 4.77 ± 3.78 years of follow-up) were included from the National Alzheimer's Coordinating Center (NACC) database. Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.

RESULTS:
A+T− males showed faster cognitive decline compared to A+T− females (p < 0.005), whereas A+T+ females showed steeper cognitive decline compared to A+T+ males (p < 0.0001). In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (p = 0.046).

DISCUSSION:
Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories. Highlights: A+T− males showed faster cognitive decline compared to A+T− females. A+T+ females showed faster cognitive decline compared to A+T+ males. Tau status significantly mediated the relationship between amyloid status and cognitive decline. Sex marginally moderated the mediating relationship between amyloid, tau, and cognitive decline. The findings point to sex differences in the impact of tau pathology on cognition.

Type de document:	Article
Mots-clés libres:	Alzheimer’s disease pathology Amyloid plaques Biomarkers Cerebrospinal fluid Cognitive decline Neurodegeneration Positron emission tomography Sex Tau tangles
Date de dépôt:	25 sept. 2026 13:16
Dernière modification:	25 sept. 2026 13:16
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/13145

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