beta-Amyloid Neurotoxicity on Basal Forebrain Cholinergic Neuron Cultures

Kim, Dong Ho; Lee, Jong Hwan; Hong, Hye Nam; Ko, Jae Young

Abstract

beta-amyloid[Abeta] peptide consisting of 40 of 42 amino acids peptide is the principal constituent of senile plaques in Alzheimer`s disease. Recently, it has been demonstrated that this peptide and its constituent fragments are toxic to neuron. Basal forebrain cholinergic neurons are preferentially damaged early in the course of Alzheimer`s disease, and the degree of cholinergic decrement correlates well with the severity of dementia. Taking into consideration of toxic properties of Abeta and the selective vulnerability of the cholinergic system, possible effects of beta-amyloid on the cultured basal forebrain cholinergic neurons were tested. Our result showed tha Abeta1-40 induced marked neurodegenerative changes including loss of cell body and dystrophic neurites in the basal forebrain neuronal cultures at 20micrometer. Immunocytochemical study showed that Abeta1-40 causes apparent loss of choline acetyltransferase[ChAT] immunoreactivity and acetycholine esterase[AchE] positive neuritic intergrity in large basal forebrain cholinegic neurons. However, the number of ChAT immunoreactive neurons was not significantly decreased as compared to other neurons in mixed culture system. These results suggest that the basal forebrain neurons are not particularly vulnearable to Abeta and that preferential injury to basal forebrain cholinergic neurons in Alzheimer`s disease may be caused by some other medchanism.