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

DS Yang, DH Small, U Seydel, JD Smith, J Hallmayer… - Neuroscience, 1999 - Elsevier
Neuroscience, 1999Elsevier
The ε4 allele of apolipoprotein E gene is a major risk factor for Alzheimer's disease.
However, the mechanism by which the E4 isoform of apolipoprotein 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 β-amyloid, we examined the
uptake of β-amyloid 1–40 into Chinese hamster ovary cells in the presence or absence of
the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E3 treatments were …
The ε4 allele of apolipoprotein E gene is a major risk factor for Alzheimer's disease. However, the mechanism by which the E4 isoform of apolipoprotein 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 β-amyloid, we examined the uptake of β-amyloid 1–40 into Chinese hamster ovary cells in the presence or absence of the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E3 treatments were associated with higher association of β-amyloid with cells as compared to treatment with E4. Heparin blocked the association of β-amyloid with cells, as did an antibody to one of the apolipoprotein E receptors (the low-density lipoprotein receptor-related protein). Thus, the apolipoproteins E2 and E3, but not E4, may play important roles in the clearance of β-amyloid from the extracellular space via the low-density lipoprotein receptor-related protein.
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