Acetylcholinesterase and its association with heparan sulphate proteoglycans in cortical amyloid deposits of Alzheimer's disease.
Previous studies have used a sensitive histochemical technique to demonstrate acetylcholinesterase and butyrylcholinesterase within the pathological lesions of Alzheimer's disease. In this study, we used this technique to show that acetylcholinesterase localized in either frozen or fixed neocortical tissue sections is removed after treatment with various glycosaminoglycans, heparinases or proteases. Heparan sulphate, heparinase lyase type I and to a lesser degree, heparin and chondroitin sulphate were effective in solubilizing a large part of the cholinesterase activity. At physiological concentrations, the protease papain or trypsin readily removed activity but collagenase or pronase were relatively less effective. Peptide protease inhibitors and divalent metals did not exhibit any clear effect. The specificity of these observations was shown by inhibition of activity with various anticholinesterases including diisofluorophosphate. Our results suggest that acetylcholinesterase is anchored to and may be released from the heparan sulphate glycosaminoglycans shown to be contained in the lesions. We further suggest that the localization of cholinesterases is closely associated with the accumulation of the glycosaminoglycans in amyloid plaques and neurofibrillary tangles.
Kalaria
R N
RN
Department of Neurology, Case Western Reserve School of Medicine, Cleveland, OH 44106.
Kroon
S N
SN
Grahovac
I
I
Perry
G
G
D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011180:Postmortem Changes; D011509:Proteoglycans / Q000032:analysis*; D012016:Reference Values
D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002795:Choline O-Acetyltransferase; D002800:Cholinesterase Inhibitors; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans