Mouse and human studies conducted by us and others suggest that a gene called MEF2C may modulate Alzheimer’s disease (AD) risk by regulating the embryonic development and/or activity of microglial cells — the “garbage collectors” of the brain. Here, we propose to use an AD mouse model wherein we inactivate MEF2C specifically in microglia, starting from early in life during embryonic development or in adulthood, in order to elucidate its role in AD pathogenesis. In doing so, we will gain insight into how and when genetic vulnerability to AD is established and how and when microglia should be targeted to ultimately slow or stop AD progression, or even delay or prevent its onset.
