Soluble and membrane-bound forms of brain acetylcholinesterase in Alzheimer's disease

In order to determine the effect of Alzheimer's disease on the relative distribution of soluble and membrane-bound molecular forms of acetylcholinesterase (AChE) in the brain, postmortem samples (delay interval less than 12 h) were obtained from parietal cortex (Brodmann area 40) and hippocampus as well as the areas containing their respective projection nuclei, i.e., substantia innominata and septal nucleus, in 9 patients with Alzheimer's disease (AD) and 4 normal controls. The monomer (G 1), dimer (G 2), and tetramer (G 4) forms of AChE were examined. In AD compared to controls, significant changes occurred in area 40 and hippocampus but not in the areas containing projection nuclei, and included loss of mean total AChE activity, decrease in the relative percentage of membrane-bound G 4, and increase in the relative percentage of soluble G 1G 2. Percent of soluble G 4 was unaffected in AD brain. In area 40 but not hippocampus a large increase in percent membrane-bound G 1-G 2 occurred. Thus, these results emphasize that the selective decrease in membrane-bound G 4 accounts for the decrease in total G 4 activity in AD brain.