Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner

The epsilon 4 allele of apolipoprotein E gene is a major risk factor for Al zheimer's a disease. However, the mechanism by which the E4 isoform of apol ipoprotein E increases the risk of Alzheimer's disease is poorly understood . To determine whether the isoform-specific effects of apolipoprotein E may be mediated via clearance of bound beta-amyloid, we examined the uptake of beta-amyloid 1-40 into Chinese hamster ovary cells in the presence or abse nce of the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E 3 treatments were associated with higher association of beta-amyloid with c ells as compared to treatment with E4. Heparin blocked the association of b eta-amyloid with cells; as did an antibody to one of the apolipoprotein E r eceptors (the low-density lipoprotein receptor-related protein). Thus, the apolipoproteins E2 and E3, but not E4, may play important roles i n the clearance of P-amyloid from the extracellular space via the low-densi ty lipoprotein receptor-related protein. (C) 1999 IBRO. Published by Elsevi er Science Ltd.