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Principal Investigator  
Principal Investigator's Name: John Melchior
Institution: Pacific Northwest National Laboratory
Department: Integrative Omics
Country:
Proposed Analysis: Both plasma and cerebrospinal fluid (CSF) contain lipid-protein complexes called lipoproteins that modulate cerebrovascular function. Brain lipoproteins (BLps) are generated de novo in the central nervous system (CNS) but relatively little is known about them, because they exist at in CSF at <0.5% the level of plasma making them notoriously difficult to isolate and study. BLps are thought to be similar to plasma high-density lipoproteins (HDL) which protects against vascular dysfunction by attenuating lipid accumulation, oxidative stress, inflammation, and apoptosis of vascular endothelial cells. HDL achieves its pleiotropic impact by deploying hundreds of compositionally distinct particle subspecies comprised of specific lipids and proteins that govern particle function. We have developed an ultra-sensitive lipoprotein profiling technology that overcomes the BLp abundance problem in CSF. Our preliminary studies show that, like plasma HDL, human BLps are highly heterogenous but contain unique populations critical for neurometabolic health. We aim to deeply characterize plasma HDL and BLps subspecies isolated from matched plasma and CSF procured from individuals afflicted with mild cognitive impairment and Alzheimer’s disease. We will group individuals based on their cognitive status and APOE genotype. We will use liquid chromatography and mass spectrometry (LC-MS/MS) to characterize the human BLp and HDL speciation profile in detail and relate it to the etiology of AD. We request access to the database to determine sample availability for our proposed NIA applications. In the event we secure funding, we will put in a full application for samples for our study.
Additional Investigators