Sex Matters: Understanding the Influence of Sex and Apolipoprotein E (APOE) Genotype on Hippocampal Plasticity and Cognition

This research centers on how sex and genetics influence brain health and cognitive decline in a model of Alzheimer’s disease (AD) risk. Although sex differences exist in many brain diseases, research targeting sex as a factor in brain health has been scarce. Here we will examine how biological sex and genotype influences the plasticity of an area of the brain called the hippocampus, which is one of the first regions affected by AD.

The hippocampus is an important area for learning and memory, and shows a great deal of capacity to change (plasticity) in adulthood. One of the unique characteristics of this plasticity in the hippocampus is adult neurogenesis (the birth of new brain cells in the adult). Recent evidence indicates that neurogenesis in the hippocampus is decreased with AD. Furthermore, inflammation appears to contribute to AD, particularly signs of inflammation in the brain, called neuroinflammation. Females show reduced neurogenesis and increased neuroinflammation that may be related to the greater lifetime risk of females to develop AD. An understanding of how neurogenesis is regulated and how inflammation in the brain is involved may provide clues for devising new therapeutic treatments for AD. We have found that biological sex influences neurogenesis in the hippocampus, and now will examine how genetic differences that increase susceptibility to AD influence this plasticity. Further, we will determine whether we can manipulate this process to improve memory and reduce neuropathology associated with AD.