Davis EJ, Solsberg CW, White CC, et al. - The X chromosome was shown to be linked with cognitive trajectories and neuropathological tau burden in aging and Alzheimer disease (AD) in a gender-specific manner. This holds significance as specific X chromosome factors could add risk or resilience to biological pathways of aging and AD in females, males, or both.

• This is a cohort analysis of 508 individuals from whom samples for RNA sequencing of the dorsolateral prefrontal cortex were collected.

• An association was found between X chromosome gene expression (evaluated by RNA sequencing) and cognitive change in women, but not in men, in a manner independent of Alzheimer disease pathology.

• In contrast, an association of X chromosome gene expression with neuropathologic tau burden was found in males but not in females.