520.10 - Longitudinal profiling of the Plasma Glycome from Normal and Alzheimer’s Disease individuals

Bryson Arnett (University of Kentucky), Tara Hawkinson (University of Kentucky), Lyndsay Young (University of Kentucky), Harrison Clarke (University of Kentucky), Michael Buoncristiani (University of Kentucky), Matthew Gentry (University of Kentucky), Ramon Sun (University of Kentucky)

Alzheimer’s disease (AD) is an incurable dementia known for its neurodegenerative pathologies including amyloid beta plaques, hyperphosphorylated neurofibrillary tau tangles, and brain glucose hypometabolism. One key metabolic pathway that also utilizes glucose is glycan synthesis, which is also known to be disrupted in AD. Glycosylation is an essential protein modification which requires glucose flux through the hexosamine pathway. Prior research in our lab has demonstrated glycosylation abnormalities can be detected in the peripheral blood of early-stage AD patients. Recently, our lab has developed effective workflows to analyze glycogen and glycan content in plasma utilizing multiple mass spectrometers, including a gas chromatography mass spectrometer (GCMS) and a matrix-assisted laser desorption/ionization-mass spectrometer imaging (MALDI-MSI). In collaboration with Biobank at the University of Kentucky, led by Dr. Pete Nelson, blood plasma samples were collected at various stages of dementia status including AD (N=2), MCI (N=2), and cognitively normal controls (N=3) over a course of 11 years. These samples were subject to metabolite extraction in preparation for GCMS and MALD-MSI analysis. Utilizing these workflows, we were able to show change in abundance of several metabolite and glycan profiles overtime in both AD and MCI patients compared to our control group. Future analyses will require larger patient cohorts and full metabolic profiling to determine glycosylation differences at various cognitive stages of disease.

National Institute of Health (NIH) grant: R01 AG066653
St Baldrickamp;rsquo;s Career Development Award
V-Scholar Grant
Rally Foundation Independent Investigator Grant