Effects of beta-amyloid on cholinergic, cholinoceptive and GABAergic neurons

Alzheimer's disease is primarily characterized by neurofibrillary tangles, senile plaques and a cholinergic hypofunction. In this study, the morpholog ical signs of toxicity of amyloid beta (A beta) 1-42 and short amyloid pept ide fragments corresponding to amino acids 31-35 and 34-39 were investigate d on cholinergic, cholinoceptive and GABAergic neuronal populations of basa l forebrain cultures. The applied A beta fragments were toxic to cholinergic, cholinoceptive and GABAergic neurons. In cholinergic and cholinoceptive neurons, the toxic eff ect caused a redistribution of the acetylcholinesterase within the cells; t he characteristic morphological changes in the GABAergic neurons involved t he fragmentation and disappearance of the processes. These results suggest that the vulnerability of neurons to A beta toxicity does not depend on their transmitter content, but the morphological manifes tation of this vulnerability differs in the various neuronal populations. T he results of experiments with short A beta fragments led to the conclusion that Leu(34) and Met(35) may be responsible for the toxicity of amyloid pe ptides.