BACKGROUND: The apolipoprotein E (apoE) type epsilon 4 isoform specifies 
increased cerebral and cerebrovascular accumulation of amyloid-beta protein (A 
beta) and contributes to the genetic susceptibility underlying a large 
proportion (approximately 60%) of typical, sporadic Alzheimer disease. 
Unfortunately, in vitro biochemical studies of direct apoE isoform-specific 
interactions with A beta 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 A beta(1-40) preferentially associates with native 
apoE of either the type epsilon 3 or the type epsilon 4 isoform.
RESULTS: Here, we demonstrate the preferential association of synthetic A 
beta(1-40) with native apoE epsilon 3. The complex between apoE epsilon 3 and A 
beta(1-40) could not be disrupted by sodium dodecyl sulfate. In a parallel 
assay, no denaturant-resistant association of A beta(1-40) with apoE epsilon 4 
was detectable.
CONCLUSIONS: These results support the notion that the apoE epsilon 4 isoform 
may foster beta-amyloidogenesis because apoE epsilon 4 is inefficient in forming 
complexes with A beta.