Sex and Gender Differences in Alzheimer's Disease - Chapter 2: Sex and sex hormone differences in hippocampal neurogenesis and their relevance to Alzheimer’s disease

Elsevier, Sex and Gender Differences in Alzheimer's Disease, 2021, Pages 23-77
Bonnie H. Lee, Tanvi A. Puri, and Liisa A.M. Galea

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that features distinctive neuropathology and global impairments to cognition. Sex differences are seen in AD, as females with AD show increased neuropathology and steeper cognitive decline than men with AD but are often neglected in the literature. The hippocampus is one of the first brain areas to be affected by AD, and this area shows a great deal of plasticity in adulthood, including neurogenesis, and is affected by both sex and sex hormones. There are sex differences in the morphology and function of the hippocampus, as well as sex differences in how the hippocampus is impacted in AD. Adult hippocampal neurogenesis has been demonstrated in humans, nonhuman primates, and rodents, and adult-born neurons play an important role in hippocampal function, including stress resilience and learning and memory. Sex hormones also affect neurogenesis and cognition, and hormone therapy has been suggested as a treatment for Alzheimer’s disease in both males and females. This chapter examines sex differences in hippocampal neurogenesis and hippocampus-dependent cognition, in both healthy individuals and in those with AD, and how these differences are affected by age, hormones, APOE genotype, and experience. Understanding the effects of sex and sex hormones on hippocampal plasticity may lead to new therapeutic targets to combat cognitive decline and neuropathology related to AD.