Differential effects of apolipoprotein E isoforms on metal-induced aggregation of Aβ using physiological concentrations

Abstract

The ε4 allele of apolipoprotein E (APOE) has been found to be a risk factor for late-onset Alzheimer's disease (AD). While the pathogenic mechanism of APOE in AD is not yet clear, APOE isoforms appear to differentially influence the aggregation of Aβ, the principal component of Alzheimer-associated β-amyloid deposits. To date, no data are available for the propensity of Aβ to aggregate in the presence of APOE under conditions where these components are at physiological concentrations (in cerebrospinal fluid, APOE and Aβ are ≃100 nM and ≃5 nM, respectively). We employed a novel in vitro filtration assay for detecting zinc(H)- and copper(II)- induced aggregation of Aβ in solutions containing c..