Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Aric F. Logsdon, Kendra L. Francis, Nicole E. Richardson, Shannon J. Hu, Chelsea L. Faber, Bao Anh Phan, Vy Nguyen, Naly Setthavongsack, William A. Banks, Randy L. Woltjer, C. Dirk Keene, Caitlin S. Latimer, Michael W. Schwartz, Jarrad M. Scarlett, Kimberly M. Alonge

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The extracellular matrix (ECM) of the brain comprises unique glycan “sulfation codes” that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate-glycosaminoglycan (CS-GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices is reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we show that patients with a clinical diagnosis of AD-related dementia undergo a re-coding of their PNN-associated CS-GAGs that correlates to Braak stage progression, hyperphosphorylated tau (p-tau) accumulation, and cognitive impairment. As these CS-GAG sulfation changes are detectable prior to the regional onset of classical AD pathology, they may contribute to the initiation and/or progression of the underlying degenerative processes and implicate the brain matrix sulfation code as a key player in the development of AD clinicopathology.

Original languageEnglish (US)
Pages (from-to)942-954
Number of pages13
JournalAlzheimer's and Dementia
Volume18
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • Alzheimer's disease
  • brain
  • chondroitin sulfates
  • cognition
  • extracellular matrix
  • glycosaminoglycans
  • mass spectrometry
  • perineuronal nets
  • tau

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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