A NEUROCHEMICAL APPROACH FOR STUDYING RESPONSE TO ACETYLCHOLINE IN ALZHEIMERS-DISEASE

The proposal of cholinomimetic treatment as a rational basis for the t herapy of Alzheimer's disease has been prematurely dismissed by some w orkers on the hypothesis of impaired coupling/signal transduction of p ostsynaptic cholinergic receptors. Disparity of reports studying such impairment may be due to inappropriate extrapolation of experimental s ystems to the physiological situation, as well as inadequate considera tion of disease epiphenoma. In the present study we have used samples with short duration of terminal coma, collected using techniques to mi nimise postmortem autolysis, and samples obtained during neurosurgery to examine carbachol stimulated hydrolysis of [H-3]phosphatidylinosito l (PI) as a marker for receptor/signal transduction integrity. The inf luence of postmortem delay was also studied using another series of sa mples and a rat model. While a significant correlation of postmortem d elay and carbachol stimulated [3H]PI hydrolysis was found, comparison of pooled neurosurgical and postmortem controls with AD samples reveal ed no significant reduction. Thus this study concurs with a similar on e previously reported here, using [3H]phosphatidylinositol 4,5-bisphos phate (1). They provide evidence for competent receptor-signal transdu ction events in AD, supporting the use of cholinomimetic therapy for d isease treatment.