Female 5xFAD mice demonstrate heightened AD-like pathology compared to males, including increased cortical Aβ plaque burden between 4 and 18 mo of age (71, 72), elevated neuroinflammation (IL-1β, TNFα, astrocyte reactivity) (73, 74), and exacerbated Aβ accumulation after perimenopause (72). This evidence concerns the gene TNF and Alzheimer disease.