Subcellular distribution of acetylcholinesterase in Alzheimer's disease: abnormal localization and solubilization

AChE activity was detected mainly in membrane-bound fractions in the frontal cortex of autopsied control or Alzheimer brain as well as rat cerebral cortex. However, the distribution of AChE among various membrane fractions was different between control and Alzheimer brains. The highest specific activity was detected in the fraction enriched with senile plaque, which was obtained from the Alzheimer brain by sonication, solubilization with detergent and centrifugation on a sucrose density gradient. The senile plaque enriched fraction was incubated with purified collagenase or protease and centrifuged at 100,000 g for 60 min. More than 50% of AChE activity was detected in the supernatant fraction. AChE in the supernatant solution showed a property of G4 isozyme. AChE might probably be anchored to the senile plaque through its collagen tail and be solubilized with collagenase or protease, producing a G4 isozyme.