Mass spectrometry-based proteomics, lipidomics and imaging reveal brain myelin changes in the neurodegenerative disorder, Nieman-Pick Type C

Modern mass spectrometry has enabled the robust measurement of biomolecules including proteins and lipids along with changes across disease states and the ability to map spatial location in situ. Our laboratory studies Niemann-Pick Type C (NPC), a fatal, neurodegenerative, lysosomal storage disorder with no FDA- approved therapy. Utilizing a combination of mass spectrometry workflows, we have identified differential proteins and lipids in a mouse model of the disease. This work focuses on the white matter regions of the cerebellum, a brain region highly affected in NPC which has both neuronal and glial cell loss. We observe decreases in phosphoinositide lipids in NPC which are crucial phospholipids for proper myelination. Additionally, our proteomic data reveal evidence for energy metabolism imbalance in NPC. This presentation will include an overview of our multi-omics approach to better understanding NPC disease and example of alterations that may reflect opportunities for monitoring during future clinical trials.