Immunohistochemical demonstration of tissue transglutaminase in amyloid plaques.
The brain of Alzheimer's disease patients contains deposits of the 39-42-amino acid (approximately 4 kDa) amyloid beta-peptide, which is derived from the beta-amyloid precursor protein. These pathological deposits have been shown to consist in part of insoluble 8- and 16-kDa aggregates of the amyloid beta-peptide. This report confirms that the amyloid beta-peptide is a substrate for tissue transglutaminase (TGase) and demonstrates that human brain preparations from Alzheimer's disease patients and control patients form cross-linked dimers from added iodinated amyloid beta-peptide. Immunohistochemical staining for TGase revealed its presence in tissue sections and isolated amyloid plaque cores obtained from brains of patients diagnosed as having Alzheimer's disease. These results provide evidence that the previously described insoluble amyloid deposits in Alzheimer's disease may involve TGase-mediated cross-linked amyloid beta-peptide polymers, and suggest a potential role for TGase in the pathogenesis of this disease.
Zhang
W
W
Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107-5563, USA.
Johnson
B R
BR
Suri
D E
DE
Martinez
J
J
Bjornsson
T D
TD
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D058225:Plaque, Amyloid / Q000201:enzymology*; D011108:Polymers / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012016:Reference Values; D013194:Staining and Labeling; D011503:Transglutaminases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D011108:Polymers; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins