Chitin-like polysaccharides in Alzheimer's disease brains

Rudy J. Castellani*, Sandra L. Siedlak, Anne E. Fortino, George Perry, Bernardino Ghetti, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The role of polysaccharides in the pathogenesis of Alzheimer disease (AD) is unclear. However, in light of studies indicating impaired glucose utilization in AD and increased activation of the hexosamine pathway that is seen with hyperglycemia, in the brains of patients with AD, aberrantly high levels of glucosamine may result in synthesis of glucosamine polymers such as chitin, a highly insoluble polymer of N-acetyl glucosamine, linearized by β1-4 linkages. To examine this further, we studied brain tissue at autopsy from subjects with sporadic and familial AD using calcofluor histochemistry. Calcofluor excites on exposure to ultraviolet light and exhibits a high affinity for chitin in vivo by interacting with β1-4 linkages. Amyloid plaques and blood vessels affected by amyloid angiopathy showed bright fluorescence. Moreover, treatment with chitinase, followed by β-N-acetyl glucosaminidase showed a decrease in calcofluor fluorescence. Since chitin is a highly insoluble molecule and a substrate for glycan-protein interactions, chitin-like polysaccharides within the brain could facilitate nucleation of amyloid proteins in various amyloidoses including AD.

Original languageEnglish (US)
Pages (from-to)419-423
Number of pages5
JournalCurrent Alzheimer Research
Volume2
Issue number4
DOIs
StatePublished - Oct 2005
Externally publishedYes

Keywords

  • Alzheimer disease
  • Amyloid
  • Chitin
  • N-acetyl glucosamine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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