Classical Alzheimer features and cholinergic dysfunction: towards a unifying hypothesis?

Objective - Our autopsy studies show possible links between classical Alzhe imer pathology and decreased expression of nicotinic acetylcholine receptor s. For further elucidation we are now using in vitro models. We report prel iminary evidence for the impact of beta -amyloid on nicotinic receptor expr ession in hippocampal dissociation culture. Methods - Cultures(Els rats) we re grown in a serum-fret: medium and incubated at 8 days in vitro for 3 day s with 1 muM AB(1) (42). Expression of alpha1 alpha7, and beta2 nicotinic r eceptor subunit protein was assessed immunohistochemically and rated semiqu antitatively. Results - A beta (1) (42) incubation resulted in a massive re duction of alpha4 protein-expressing neurons, this effect was less pronounc ed for the alpha7 and beta2 subunit protein. Conclusion - These findings pr ovide first evidence for a direct impact of classical Alzheimer pathology f eatures on nicotinic receptor expression in vitro. Our model will be useful for testing the potential of drugs to stop or reverse these effects.