APOLIPOPROTEIN-E AND CHOLESTEROL AFFECT NEURONAL CALCIUM SIGNALING - THE POSSIBLE RELATIONSHIP TO BETA-AMYLOID NEUROTOXICITY

Besides the neurotoxic properties of beta-amyloid (beta A4), apolipopr otein E polymorphism seems to play an important role in the pathogenes is of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mo use brain neurons and human lymphocytes was nearly abolished by choles terol (100-500 mu mol/l). This effect may be related to the membrane s tabilizing properties of cholesterol which could be confirmed by measu rements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response signif icantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calc ium amplifying effect of ApoE itself as well as by the modulation of b eta A4 neurotoxicity by cholesterol. (C) 1994 Academic Press, Inc.