A Comprehensive LC-MS Metabolomics Approach Reveals a Novel Panel of Markers in an APOE4 Mouse Model of Alzheimer’s Disease

Overview

APOE is a mediator of lipid metabolism and allele APOE4 is the strongest genetic risk factor for Alzheimer's disease. One copy of the allele increases likelihood for Alzheimer's by three -fold while possessing two - copies of the allele increases the chances by up to 15-fold. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to dev elop preventative therapeutics for carriers. To gain insight on the molecular impact of APOE4 over time, liquid chromatography -mass spectrometry (LC- MS) untargeted metabolomics analysis of cerebellum tissue samples at 6, 12, 18, and 21 months from both E3 and E4 mice was conducted and analyzed. Results have identified four downregulated and one upregulated metabolic marker at 21 months, which provide evidence in support of APOE4 as an inhibitor of normal function. Furthermore, metabolic profiles across the mouse life span as well between males and females at each time point was compared to assess the molecular changes caused by APOE4 and gain further insight into the mechanism by which the allele increases susceptibility for Alzheimer’s disease.

Competition history

• JSHS 2024 Category not listed

Resources

• National JSHS abstract book ↗

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