Abstract by Russell Denton
Chemistry and Biochemistry
The Affects of Apolipoprotein E on Alzheimer’s Disease Development
A strong genetic predictor of Alzheimer’s disease (AD) risk is the lipid transporter Apolipoprotein E (ApoE). Relative to the ApoE isoform 3, isoform 2 protects against AD, but isoform 4 predisposes AD risk when effects on transcription, and lipid or protein transport are considered. A leading hypothesis suggests lipid and protein transport is biased in healthy subjects’ brains, which sensitizes or protects these individuals against AD related stresses. The complex interplay of genetic and environmental risk factors indicates that the preexisting metabolic condition of the brain is the key initiating variable. Understanding this interlay is crucial to finding a viable method for treating or preventing AD. We are considering which AD related metabolic pathways are most effected by the ApoE isoforms. We are using kinetic and quantitative proteomics to compare protein and lipid metabolism observed in the brains of ApoE isoform variant mice. The goal is to identify metabolic biases which protect against or predispose individuals to AD.