A meta-analysis of six longitudinal studies found that among individuals with high beta-amyloid levels, women accumulate tau at a significantly faster rate than men, particularly in brain regions associated with memory and cognition.

Rsearchers analyzed tau positron-emission tomography data from 1,376 cognitively unimpaired individuals (55% female; mean age = 71.9 years) followed for a mean of 2.8 years. Among them, 29% had high beta-amyloid (Aβ) at baseline, and 30% carried the APOEε4 allele, a known genetic risk factor for Alzheimer's disease (AD). Their findings were published in JAMA Neurology.

Women with elevated Aβ demonstrated significantly faster tau accumulation than men in key regions, including the inferior temporal lobe, temporal fusiform gyrus, and lateral occipital cortex.

Sex differences were also evident among APOEε4 carriers, with women showing faster tau accumulation in the inferior temporal gyrus than male carriers, reinforcing prior evidence of a stronger pathological effect of the allele in women.

The study extends previous cross-sectional findings by providing robust longitudinal evidence that Aβ deposition is associated with sex-specific risk for downstream accumulation of tau. "Females with high baseline Aβ exhibited substantially faster tau accumulation relative to male individuals with high baseline Aβ," wrote the study's authors.

They continued, "Sex differences in the pathological progression of AD call for sex-specific timing considerations when administrating anti-Aβ and anti-tau treatments." This conclusion has implications for clinical trials and treatment strategies, especially as new monoclonal antibody treatments for AD become available.

Full disclosures of the authors are available in the study.