Abstract by Joe Creery
John C. Price
Chemistry and Biochemistry
Identifying ApoE isoform-dependent changes for protein turnover in the brain
It is known that a significant contributor to proteopathy in late-onset Alzheimer’s disease (AD) is the genetic variation of Apolipoprotein E (ApoE). There is evidence to support that relative to isoform 3, isoform type 4 is implicated in increased AD risk, and isoform 2 protects against AD. Although this is known, there is no clear picture of total protein homeostasis and turnover in the presence of the different isoforms of ApoE. Comparing transgenic mice (C57BL/6), expressing one of the three isoforms of human ApoE, we can observe differences in relative concentrations of proteins that do not directly interact with ApoE on a protein-protein level. Along with protein concentration measurements we apply newly developed methods to measure the turnover rate of each protein. Because AD is an age-related disease with a genetic factor like ApoE we hypothesize that the metabolic environment created by ApoE 4 can be observed in our young mice without them showing the disease until later. We also have received data for ApoE 4 mice that have been dietary restricted which we hypothesize will make contributions to reverse the metabolic damage created by ApoE 4.