Lewis Honors College Capstone Collection

Year of Publication

2016

College

Agriculture, Food and Environment

Department/School/Program

Medical Sciences

Degree Name

B.S. in Agricultural and Medical Biotechnology

First Capstone/Thesis Advisor

Steven Estus

Abstract

Increased Alzheimer’s disease (AD) risk has previously been associated with a SNP called rs610932 near the gene MS4A6A. The goal of this experiment was to quantify the expression of two MS4A6A isoforms in the brains of AD and non-AD subjects, particularly as a function of rs610932 genotype. According to an article titled “Alzheimer’s Disease Susceptibility Variants in the MS4A6A Gene are Associated with Altered Levels of MS4A6A Expression in Blood”, MS4A6A has four different isoforms that have been reported to be differentially expressed in the blood of AD subjects compared to non-AD subjects (Petroula et al., 2014). After statistically analyzing the association between two of the MS4A6A variants, Isoform 6 (total MS4A6A transcript) and a variant, Isoform 4, and rs610932 using AD status and microglial expression as independent variables, we found significant expression differences in AD and non-AD subjects in the brain for the Isoform 4. We did not detect significant expression differences for Isoform 6 in AD subjects, nor did we find significant expression differences in either isoform as a function of the rs610932 SNP. These results are in contrast to previous findings that suggested a significant expression difference due to rs610932 in whole blood (Petroula et al., 2014). In summary, further work is necessary to understand how rs610932 modulates MS4A6A to alter AD risk.

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