Chitin-like polysaccharides in Alzheimer's disease brains.
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 beta1-4 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 beta1-4 linkages. Amyloid plaques and blood vessels affected by amyloid angiopathy showed bright fluorescence. Moreover, treatment with chitinase, followed by beta-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.
Castellani
Rudy J
RJ
Department of Physiology (Human Pathology), Michigan State University, East Lansing, MI, USA. rcastellani@hsc.wvu.edu
Siedlak
Sandra L
SL
Fortino
Anne E
AE
Perry
George
G
Ghetti
Bernardino
B
Smith
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001557:Benzenesulfonates; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology*; D002686:Chitin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016874:Neurofibrillary Tangles / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001557:Benzenesulfonates; D016875:tau Proteins; D002686:Chitin; C007061:C.I. Fluorescent Brightening Agent 28