BETA-AMYLOID INDUCED INCREASE IN CHOLINE FLUX ACROSS PC12 CELL-MEMBRANES

Beta-amyloid peptide is the main constituent of senile plaques and is implicated in the pathogenesis of Alzheimer's disease. It has been sho wn to be both neurotoxic and neurotrophic in vivo, and its effects hav e been suggested to be mediated in part by alterations in membrane tra nsport. In the present study, we investigated the effect of beta-amylo id (1-40) on choline transport in cultured PC12 cells. We found that e xposure to 46 or 92 mu M beta-amyloid (1-40) increased [C-14]choline f lux in PC12 cells in a concentration-dependent manner, whereas exposur e to reverse sequence beta-amyloid (40-1) had no effect. If there is a similar effect in vivo, the increased beta-amyloid dependent permeabi lity to choline could lead to depletion of cellular choline stores and could contribute to the selective vulnerability of cholinergic neuron s in Alzheimer's disease. (C) 1997 Elsevier Science Ireland Ltd.