A neurochemical approach for studying response to acetylcholine in Alzheimer's disease.
The proposal of cholinomimetic treatment as a rational basis for the therapy of Alzheimer's disease has been prematurely dismissed by some workers on the hypothesis of impaired coupling/signal transduction of postsynaptic cholinergic receptors. Disparity of reports studying such impairment may be due to inappropriate extrapolation of experimental systems to the physiological situation, as well as inadequate consideration of disease epiphenoma. In the present study we have used samples with short duration of terminal coma, collected using techniques to minimise postmortem autolysis, and samples obtained during neurosurgery to examine carbachol stimulated hydrolysis of [3H]phosphatidylinositol (PI) as a marker for receptor/signal transduction integrity. The influence of postmortem delay was also studied using another series of samples and a rat model. While a significant correlation of postmortem delay and carbachol stimulated [3H]PI hydrolysis was found, comparison of pooled neurosurgical and postmortem controls with AD samples revealed no significant reduction. Thus this study concurs with a similar one previously reported here, using [3H]phosphatidylinositol 4,5-bisphosphate (1). They provide evidence for competent receptor-signal transduction events in AD, supporting the use of cholinomimetic therapy for disease treatment.
D000109:Acetylcholine / Q000502:physiology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002217:Carbachol / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009493:Neurosurgery; D010716:Phosphatidylinositols / Q000378:metabolism*; D011180:Postmortem Changes; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology*; D012016:Reference Values; D015398:Signal Transduction / Q000502:physiology
D015415:Biomarkers; D018678:Cholinergic Agents; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine