The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease

J Neurochem. 2021 Oct;159(2):292-304. doi: 10.1111/jnc.15202. Epub 2020 Oct 24.


Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation. Still, the roles of glycans in the development of AD are relatively unexplored. Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls. As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain. Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain. Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain. All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc). The glycans that were altered in AD brain differed from those that were altered in AD CSF. One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid. Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.

Keywords: Alzheimer disease; N-glycan; frontal cortex; glycomics; hippocampus; mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Asparagine / metabolism
  • Brain Chemistry*
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / metabolism*
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Epitopes
  • Female
  • Fucose / metabolism
  • Galactose / metabolism
  • Glycoproteins / metabolism
  • Hippocampus / chemistry
  • Hippocampus / metabolism*
  • Humans
  • Male
  • N-Acetylneuraminic Acid / metabolism
  • Polysaccharides / metabolism*
  • Tandem Mass Spectrometry


  • Epitopes
  • Glycoproteins
  • Polysaccharides
  • Fucose
  • Asparagine
  • N-Acetylneuraminic Acid
  • Acetylglucosamine
  • Galactose