Differential Gene Expression Analysis of APOE-ε3 and APOE-ε4 Pericyte Homozygotes

Abstract

Alzheimer’s disease affects nearly one in ten individuals living in the United States over the age of 65, a leading cause of death and adult morbidity in the nation with no cure. While many risk factors for the progressive neurological disorder are known, the biomolecular mechanisms underlying the most significant genetic indicator of susceptibility, the apolipoprotein E4 allele (APOE-ɛ4), have not been fully characterized in pericytes, a cell type that plays a role in maintaining the integrity of the blood-brain barrier (BBB). Studies have suggested apolipoprotein E4 (apoE4) is associated with increased levels of cytotoxic protein amyloid beta (Aβ) in some regions of the brain, cellular phenotypic changes in the neurovascular unit that inhibit Aβ clearance, and degradation of the BBB, all of which have been known to increase the risk of Alzheimer’s disease and other neurological disorders. Here we analyze RNA sequencing data published by the Tsai group to identify the most differentially expressed genes in homozygotic APOE-ɛ3 and APOE-ɛ4 pericytes, and use Qiagen’s Ingenuity® Pathway Analysis software to determine the downstream biological impacts of apoE4, mechanistic differences as compared to apoE3, potential therapeutic targets, and avenues for future experimentation.