Sex Differences in Alzheimer’s Biomarkers Linked to Faster Cognitive Decline

Sex differences in Alzheimer’s disease present ongoing diagnostic challenges, with women often experiencing a disproportionate disease burden even when preclinical amyloid-beta levels are similar to men. A new study shows that women exhibit greater tau abnormalities and faster cognitive decline than men when amyloid is elevated. Researchers now outline longitudinal biomarker and imaging patterns that underscore the need for sex-aware assessment approaches.

A multinational team investigated a biomarker-led approach centered on plasma phosphorylated tau 217 (p-tau217) in the context of amyloid-β (Aβ) positivity, integrating positron emission tomography (PET) to visualize Aβ plaques and tau tangles and incorporating a cognitive endpoint. The cognitive assessment used the Preclinical Alzheimer Cognitive Composite (PACC) to quantify memory and thinking performance. Together, these modalities were used to map early biological changes and their cognitive consequences by sex.

The analysis pooled 1,200 participants across five major datasets, comprising one clinical trial and four observational cohorts. Investigators measured blood p‑tau217, performed PET imaging for Aβ and regional tau, and tracked cognition longitudinally. Follow‑up spanned several years, with brain imaging assessed over a mean 3.6 years and cognitive performance over 4.6 years, enabling comparisons of trajectories between women and men.

Results showed that when Aβ levels were high, women had significantly higher plasma p‑tau217 than men; this sex difference did not appear at low Aβ levels. For any given blood p‑tau217 level, women exhibited faster accumulation of tau tangles in multiple regions, including the parietal cortex, middle frontal gyrus, and precuneus. Consistent with these biological differences, women experienced faster cognitive decline, though at lower p‑tau217 levels they tended to perform better on cognitive testing than men. The study was published in JAMA Neurology on February 16, 2026.

The authors concluded that women respond differently at a biological level to early Alzheimer’s triggers and recommended that clinical care consider sex‑specific biomarker thresholds to improve identification and monitoring of women at risk. These data underscore the potential value of calibrating blood p‑tau217 interpretation by sex and Aβ status to better align laboratory readouts with disease biology and cognitive outcomes.