ABNORMALITIES OF ACETYLCHOLINESTERASE IN ALZHEIMERS-DISEASE WITH SPECIAL REFERENCE TO EFFECT OF ACETYLCHOLINESTERASE INHIBITOR

In brains from Alzheimer's disease patients, a high activity of acetyl cholinesterase (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, tetr ahydroaminoacridine (THA) and Nicergoline had a poor effect on AChE pr esent 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 pur ified from rat brain (G4 form) or from human erythrocytes (G2 form). E -2020 inhibited all 3 types of isozymes more effectively than physosti gmine, amiridine, Nicergoline or THA. The inhibitory effect of AChE in hibitors on AChE solubilized from senile plaque was also small as comp ared with AChE in normal human brain, rat brain, human erythrocytes or rat skeletal muscle. These results suggest that the characteristics o f AChE present in senile plaques are abnormal or different from that i n normal brain or skeletal muscle. As AChE in the Alzheimer brain seem s to contain a higher degree of glycosylation, the hydrophobic propert y of anomalous AChE may serve a seed of amyloid fibril in senile plaqu es.