(680.8) A human prefrontal cortex tissue microarray to study Alzheimer’s disease

Poster Board Number: A483

Rikke Nielsen (University of Kentucky), Tara Hawkinson (University of Kentucky), Harrison Clarke (University of Kentucky), Lyndsay Young (University of Kentucky), Peter Nelson (University of Kentucky), Matthew Gentry (University of Kentucky), Ramon Sun (University of Kentucky)

Alzheimer’s disease (AD) is characterized by proteinopathy, glucose hypometabolism, progressive neurodegeneration and eventually death from organ failure. One of the disease characteristics is glucose hypometabolism in the brain that can lead to perturbed cerebral glycan and glycogen metabolism. A key driver of disrupted glucose metabolism could be linked to glycans, which is a co-translational modification of proteins involved in various biological functions of the cell. Prior research has demonstrated profound glycosylation differences in AD tissue compared to normal tissue, however, these differences have yet to be linked to disease progression. In collaboration with AD biobank at the University of Kentucky led by Dr. Peter Nelson, human AD brain tissue samples from over 90 deceased patients with and without known cognitive impairment were collected, in addition to their corresponding metadata. To analyze the N-linked glycan content of the samples a Tissue Microarray (TMA) was produced using cores punched from the patients’ cortex tissue, and run through an optimized, enzyme-assisted matrix-assisted laser desorption/ionization-mass spectrometer imager (MALDI-MSI) workflow. Our data not only revealed interesting correlations between glycosylation and disease pathology of AD but also interesting differences in the glycan profiles between male and female patients. Further indepth analyses will be required to further determine specific markers for the correlation between glycosylation and disease progression of AD.

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