This meta-analysis investigated whether females show faster tau accumulation than males in the context of high β-amyloid (Aβ) levels, a hallmark of Alzheimer disease (AD), and whether sex influences the relationship between APOEε4 status and tau buildup. Using longitudinal data from six major aging and AD studies, researchers analyzed tau-PET and Aβ-PET scans in 1,376 participants. The findings revealed that, among individuals with elevated Aβ, females showed faster tau accumulation than males, particularly in the inferior temporal, temporal fusiform, and lateral occipital brain regions. Additionally, among APOEε4 carriers, women again exhibited more rapid tau buildup in the inferior temporal cortex. These results support the growing evidence that females are more susceptible to tau pathology progression in AD, especially when Aβ is present or in those with genetic risk factors like APOEε4. The study highlights the importance of considering sex differences in disease progression and suggests the need for sex-specific approaches to the timing of anti-Aβ and anti-tau treatments in Alzheimer’s disease.
Author(s):
Gillian T. Coughlan, Hannah M. Klinger, Rory Boyle et al.
References including authors:
Coughlan GT, Klinger HM, Boyle R, Betthauser TJ, Binette AP, Christenson L, et al.; Alzheimer’s Disease Neuroimaging Initiative. Sex differences in longitudinal tau‑PET in preclinical Alzheimer disease: a meta‑analysis. JAMA Neurol. 2025 Mar 3;82(4):364–75. doi:10.1001/jamaneurol.2025.0013.