Chitin-like polysaccharides in Alzheimer's disease brains

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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

Fingerprint

Chitin
Polysaccharides
Alzheimer Disease
Glucosamine
Brain
Polymers
Fluorescence
Amyloidogenic Proteins
Hexosamines
Hexosaminidases
Chitinases
Amyloid Plaques
Amyloidosis
Ultraviolet Rays
Hyperglycemia
Blood Vessels
Autopsy
Glucose
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Castellani, R. J., Siedlak, S. L., Fortino, A. E., Perry, G., Ghetti, B., & Smith, M. A. (2005). Chitin-like polysaccharides in Alzheimer's disease brains. Current Alzheimer Research, 2(4), 419-423. https://doi.org/10.2174/156720505774330555

Chitin-like polysaccharides in Alzheimer's disease brains. / Castellani, Rudy J.; Siedlak, Sandra L.; Fortino, Anne E.; Perry, George; Ghetti, Bernardino; Smith, Mark A.

In: Current Alzheimer Research, Vol. 2, No. 4, 10.2005, p. 419-423.

Research output: Contribution to journalArticle

Castellani, RJ, Siedlak, SL, Fortino, AE, Perry, G, Ghetti, B & Smith, MA 2005, 'Chitin-like polysaccharides in Alzheimer's disease brains', Current Alzheimer Research, vol. 2, no. 4, pp. 419-423. https://doi.org/10.2174/156720505774330555
Castellani, Rudy J. ; Siedlak, Sandra L. ; Fortino, Anne E. ; Perry, George ; Ghetti, Bernardino ; Smith, Mark A. / Chitin-like polysaccharides in Alzheimer's disease brains. In: Current Alzheimer Research. 2005 ; Vol. 2, No. 4. pp. 419-423.
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