NEW imaging research shows that women in their 60s carry a higher burden of Alzheimer’s pathology than men, despite retaining better brain structure. This apparent dissociation between pathology and neurodegeneration could help explain why women often present with symptoms later despite higher underlying disease burden.
Sex Differences in Alzheimer’s Disease Biomarkers in Midlife
Alzheimer’s disease biomarkers are increasingly used to detect early pathological changes before cognitive symptoms appear. However, much of the existing evidence is based on older or less diverse populations. Understanding whether biological sex influences these biomarkers earlier in life could improve risk stratification and inform more personalised approaches to dementia prevention.
Researchers addressed this gap by examining adults aged 60 to 69 years without cognitive impairment from a racially and ethnically diverse, community-based cohort in New York City. The focus was on whether Alzheimer’s disease biomarkers differed between women and men during the seventh decade of life, independent of known genetic and vascular risk factors.
Imaging Results Reveal Diverging Alzheimer’s Disease Biomarkers
The cross-sectional study included 503 participants with a mean age of 64.6 years, of whom 63.8% were women. Using PET and MRI imaging, investigators assessed amyloid burden, tau deposition across Braak stages I to VI, cortical thickness in Alzheimer’s signature regions, and white matter hyperintensity volumes.
Women demonstrated significantly greater amyloid burden than men, with B = 0.05 (95% CI, 0.02-0.07; P < .001). Tau burden was also higher in women across Braak stages III and IV (B = 0.05; 95% CI, 0.02-0.08; P = .003) and Braak stages V and VI (B = 0.09; 95% CI, 0.06-0.12; P < .001). Despite this increased pathology, women showed greater cortical thickness in Alzheimer’s signature regions (B = 0.04; 95% CI, 0.02-0.05; P < .001). Notably, sex differences in tau burden were more pronounced among APOE ε4 carriers, particularly in early to middle Braak stages. All results remained significant after false discovery rate correction.
Clinical Implications and Future Directions
These findings suggest that women may accumulate Alzheimer’s disease biomarkers earlier or more extensively than men, while also demonstrating greater structural brain resilience. For clinical practice, the results highlight the importance of considering sex-specific trajectories when interpreting Alzheimer’s disease biomarkers, particularly in midlife populations and genetic risk carriers. Future longitudinal studies are needed to determine how these differences influence symptom onset, progression, and response to emerging disease-modifying therapies.
Reference
Akinci M et al. Sex differences in Alzheimer disease imaging biomarkers in a diverse, community-based cohort. JAMA Netw Open. 2026;9(1):e2554524.
