CHOLESTEROL AFFECTS NEURONAL CALCIUM SIGNALING - A POSSIBLE LINK BETWEEN APOLIPOPROTEIN POLYMORPHISM, BETA-AMYLOID NEUROTOXICITY, AND NEURODEGENERATION IN ALZHEIMERS-DISEASE

The findings that the beta-amyloid (beta A4) peptide possesses neuroto xic properties represents a possible link between beta A4 formation an d neurodegeneration in Alzheimer's disease (AD). One possible mechanis m of beta A4's neurotoxic properties in its direct effect on fluidity measures of mouse, rat, and human brain membranes, indicating that/bet a A4 disturbs or even disrupts membrane structure and/or integrity. Al tering membrane cholesterol not only directly affects calcium signalli ng of central neurons bur also modulates the effect of beta A4. It is suggested that changes of cholesterol distribution in the brain may re present one possible link between beta A4 induced neurodegeneration an d Apolipoprotein E polymorphism as one of the genetic risk factors of AD. (C)1997, Medikal Press.