Cardiovascular Response to ApoE4 Fragmentation
Dr. Julia Oxford and Dr. Troy Rohn
Apolipoprotein-E4 is one of three alleles of the human apolipoprotein-E (APOE) gene; each allele of the gene differs by one amino acid residue-a progressive swap from C112, C158 in ApoE2 to C112, R158 in APOE3, then R112, R158 in APOE4. The APOE4 allele has been recognized over the past 20 years as the largest genetic contributing factor in developing late-onset Alzheimer’s disease (LoAD) whereas the APOE3 allele shows no increase in risk despite only differing by a single amino acid residue. In addition to this relationship with AD, inheritance of the APOE4 allele has also been a known contributor to increased risk of cardiovascular disease (CD). Our current model-zebrafish (Danio rerio)- has been used to identify potential toxic effects of a 151 amino acid amino-terminal protein modeled after a 17kDa ApoE4 protein fragment (nApoE41-151). The nApoE41-151 fragment was identified in human AD post-mortem frontal cortex tissue and has shown to be cytotoxic in both BV2 cell culture and in zebrafish by the Rohn Lab. Our data has indicated that there is a cardiovascular effect during embryogenesis to nApoE41-51 and leads to increased prevalence of enlarged hearts and pericardial edemas. Our project aim is to identify potential cardiovascular actions of nApoE41-51 in zebrafish embryos and to compare these possible effects with a similar nApoE31-151 fragment as a control.
Ercanbrack, Wesley; Preston, Madyson; Oxford, Julia; and Rohn, Troy, "Cardiovascular Response to ApoE4 Fragmentation" (2020). 2020 Undergraduate Research Showcase. 51.