Abstract by Isabella James
Chemistry and Biochemistry
Desorption Electrospray Ionization (DESI) and Dielectric Barrier Discharge (DBD) Ionization Mass Spectrometry Imaging of Lipid Metabolism in Alzheimer’s Disease
The strongest genetic and behavioral risk factors for Alzheimer’s disease (AD) are associated with lipid metabolism. The APOE protein regulates lipid transport and homeostasis and has multiple isoforms that are associated with AD risk. The APOE2 isoform has a protective effect against AD, APOE3 is neutral, and APOE4 increases risk for AD. Cholesterol levels are also an important risk factor in AD development. Because anatomically distinct structures in the brain have different susceptibilities to AD, we use desorption electrospray ionization (DESI) mass spectrometric imaging in conjunction with metabolic labeling to detect differences in the spatial distributions and turnover rates of various lipids in different parts of the brain. Because cholesterol is an important risk factor for AD and because it is difficult to ionize with DESI, we are developing a dielectric barrier discharge (DBD) ionization source to image spatially resolved concentration and turnover of cholesterol in the brain. Identifying differences between APOE isoforms with mass spectrometry imaging will allow us to identify patterns of lipid metabolism that may contribute to AD.