Sex differences in Alzheimer’s disease animal models

Alzheimer’s disease (AD) is the most prevalent of all neurodegenerative disorders. Distinct protein inclusions, amyloid-β (Aβ) plaques, and neurofibrillary tangles (NFTs) characterize the AD brain. Several epidemiological studies have shown dissimilarities in AD when sex is considered, which has driven the scientific community, over the years, to consider sex as a determinant factor in AD pathology. Similarly, studies in animal models have been moving forward to investigate the genetic and metabolic basis of sex differences in AD for the development of possible new sex-specific therapeutic strategies. However, sex differences are still poorly understood, and preclinical studies should increasingly consider the relevance of such disparities. So far, most findings have pointed to sex differences in murine transgenic genetic backgrounds and dependently on age. Other studies have found sex-dependent AD pathological hallmarks within different rodent models. Hence, studies aiming to understand AD pathogenesis, diagnostic and prognostic criteria, and response to therapy must include the study of sex. In this chapter, we describe the state of the art behind the sex differences in AD so far, and discuss preclinical aspects considered in these studies.