Neurodegenerative diseases (ND) such as: Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis have been linked with environmental exposures to numerous chemicals within a background of genetic risk factors. However, the exact role of environmental agents and the establishment of markers of disease have remained elusive;particularly, early markers that occur prior to disease onset. For ND diseases such as Parkinson's, oxidative stress and mitochondrial dysfunction are known contributing factors and the lipid rich regions of the brain which are critical for neuronal functin are sensitive targets, playing a key role in disease etiology. Localized lipid concentrations offer important information on the functional state and molecular pathobiology of ND. Traditional molecular biology techniques, such as in situ hybridization and immunohistochemistry, are ideally suited for characterization of mRNA and protein abundances while mass spectrometry imaging (MSI) enables identification and spatial localization of individual lipids and metabolites in tissues thereby providing important complementary information. This project is focused on the development of a complementary mass spectrometry-based platform for quantitative imaging of lipids and metabolites in tissues with high spatial resolution and high sensitivity for obtaining molecular markers of the early disease stages at a cellular level. This capability is critical to advancing the molecular level understanding of the effect of environmental chemical exposure on neurodegeneration.