期刊
ALZHEIMERS & DEMENTIA
卷 18, 期 10, 页码 1721-1735出版社
WILEY
DOI: 10.1002/alz.12523
关键词
bioenergetics; carbohydrate metabolism; MALDI imaging; neuronal function; N-linked glycosylation; synaptic transmission
资金
- National Institutes of Health [R35NS116824, P01 NS097197, R01AG066653]
- University ofKentucky Markey CancerCenter [P30CA177558]
The study identified robust regional-specific N-linked glycan changes associated with Alzheimer's disease in both mice and humans, suggesting that N-linked glycan dysregulation could be an underpinning of AD pathologies.
N-linked protein glycosylation in the brain is an understudied facet of glucose utilization that impacts a myriad of cellular processes including resting membrane potential, axon firing, and synaptic vesicle trafficking. Currently, a spatial map of N-linked glycans within the normal and Alzheimer's disease (AD) human brain does not exist. A comprehensive analysis of the spatial N-linked glycome would improve our understanding of brain energy metabolism, linking metabolism to signaling events perturbed during AD progression, and could illuminate new therapeutic strategies. Herein we report an optimized in situ workflow for enzyme-assisted, matrix-assisted laser desorption and ionization (MALDI) mass spectrometry imaging (MSI) of brain N-linked glycans. Using this workflow, we spatially interrogated N-linked glycan heterogeneity in both mouse and human AD brains and their respective age-matched controls. We identified robust regional-specific N-linked glycan changes associated with AD in mice and humans. These data suggest that N-linked glycan dysregulation could be an underpinning of AD pathologies.
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