Abnormalities of acetylcholinesterase in Alzheimer's disease with special reference to effect of acetylcholinesterase inhibitor.
In brains from Alzheimer's disease patients, a high activity of acetylcholinesterase (AChE) was detected in the senile plaque-rich fraction and its isozyme pattern was mainly type A, containing a collagen-like tail. AChE inhibitors, including physostigmine, E-2020, amiridin, tetrahydroaminoacridine (THA) and Nicergoline had a poor effect on AChE present in the senile plaque-rich fraction isolated from Alzheimer brain than that either in the soluble fraction of Alzheimer brain or in the control brain. However, AChE purified from rat skeletal muscle (type A) was significantly more susceptible to AChE inhibitors than that purified from rat brain (G4 form) or from human erythrocytes (G2 form). E-2020 inhibited all 3 types of isozymes more effectively than physostigmine, amiridine, Nicergoline or THA. The inhibitory effect of AChE inhibitors on AChE solubilized from senile plaque was also small as compared with AChE in normal human brain, rat brain, human erythrocytes or rat skeletal muscle. These results suggest that the characteristics of AChE present in senile plaques are abnormal or different from that in normal brain or skeletal muscle. As AChE in the Alzheimer brain seems to contain a higher degree of glycosylation, the hydrophobic property of anomalous AChE may serve a seed of amyloid fibril in senile plaques.
Mimori
Y
Y
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Nakamura
S
S
Yukawa
M
M
D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D007527:Isoenzymes; D000110:Acetylcholinesterase