Research Plan - The effect of APOE genotype on microglial-mediated synapse loss in AD

Abstract

This is a pre-registration of an experimental plan to examine the effect of APOE genotype on microglial-mediated synapse loss in Alzheimer's disease. There is now extensive literature covering synapse loss in AD and mouse studies have shown microglia are key players in aberrantly clearing synapses during AD. From this pilot study, we expect to establish the effect size of engulfed synaptic elements inside microglial cells, and investigate if having AD, and particularly being an APOE4 carrier, affects this process. As APOE4 carriers are more likely to develop AD and have an earlier AD onset, we postulate that microglia are activated and primed for synapse phagocytosis, with e4 individuals' microglia internalizing more synapses and amyloid beta. We also hypothesize that microglia around plaques, being more reactive, will phagocytose synapses more than microglia away from plaques.