Alzheimer amyloid-β peptide forms denaturant-resistant complex with type ε3 but not type ε4 isoform of native apolipoprotein E

Abstract

Background: The apolipoprotein E (apoE) type ε4 isoform specifies increased cerebral and cerebrovascular accumulation of amyloid-β protein (Aβ) and contributes to the genetic susceptibility underlying a large proportion (~60%) of typical, sporadic Alzheimer disease. Unfortunately, in vitro biochemical studies of direct apoE isoform-specific interactions with Aβ have been inconsistent, perhaps due to the use by different research groups of apoE isoform preparations in different conformational states (purified denatured versus native). Materials and Methods: In the current study, we have investigated the possibility that synthetic Aβ1-40 preferentially associates with native apoE of either the type ε3 or the type ε4 isoform. Results: Here, we demonstrate the preferential association of synthetic Aβ1-40 with native apoE ε3. The complex between apoE ε3 and Aβ1-40 could not be disrupted by sodium dodecyl sulfate. In a parallel assay, no denaturant-resistant association of Aβ1-40 with apoE ε4 was detectable. Conclusions: These results support the notion that the apoE ε4 isoform may foster β-amyloidogenesis because apoE ε4 is inefficient in forming complexes with Aβ.