Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity

Besides the neurotoxic properties of beta-amyloid (beta A4), apolipoprotein E polymorphism seems to play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mouse brain neurons and human lymphocytes was nearly abolished by cholesterol (100-500 mumol/l). This effect may be related to the membrane stabilizing properties of cholesterol which could be confirmed by measurements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response significantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calcium amplifying effect of ApoE itself as well as by the modulation of beta A4 neurotoxicity by cholesterol.