The role of ApoE in Alzheimer disease and in traumatic brain injury

The objective of the proposed research is to determine how ApoE4 upregulates mitochondria-associated endoplasmic reticulum membranes. The investigators will compare ApoE4 vs ApoE3 effects on mitochondria-associated endoplasmic reticulum membrane function following both pharmacological and genetic perturbations of candidate proteins involved in cholesterol homeostasis. They will also use comparative transcriptomics and lipidomics to identify pathways that are differently affected by ApoE4 vs ApoE3. They will determine whether cholesterol homeostasis plays a role in the ApoE4-mediated upregulation of mitochondria-associated endoplasmic reticulum membrane function. In addition they hypothesize that ApoE may also affect mitochondria-associated endoplasmic reticulum membrane via pathways that are unrelated to cholesterol homeostasis. The transcriptomic and lipidomics experiments should reveal other pathways that affect mitochondria-associated endoplasmic reticulum membranes.