Emerging genetic, epidemiological, and cell biological data has implicated lipid and cholesterol metabolism in a variety of neurodegenerative diseases. However, lipid biology remains an understudied area of research, and there are technical complexities with the application of lipidomic methods to human tissues. This project will analyze the lipidome of human iPSC-derived neurons and glia, gene-edited for specific disease variants. In addition, through screening of small molecules and organelle specific analysis of lipid changes, the project will identify pathways that underlie pathogenic lipid changes in neurodegenerative diseases. Overall, the project will generate the first map of disease-specific, genotype-specific and cell type-specific changes in the human lipidome associated with neurodegenerative diseases.
This project was selected for the second phase of the Collaborative Pairs RFA.