ALZHEIMER AMYLOID-BETA PEPTIDE FORMS DENATURANT-RESISTANT COMPLEX WITH TYPE EPSILON-3 BUT NOT TYPE EPSILON-4 ISOFORM OF NATIVE APOLIPOPROTEIN-E

Background: The apolipoprotein E (apoE) type epsilon 4 isoform specifi es increased cerebral and cerebrovascular accumulation of amyloid-beta protein (A beta) and contributes re, the genetic susceptibility under lying a large proportion (similar to 60%) of typical, sporadic Alzheim er disease. Unfortunately, in vitro biochemical studies of direct apoE isoform-specific interactions with A beta have been inconsistent, per haps due to the use by different research groups of apoE isoform prepa rations in different conformational states (purified denatured versus native). Materials and Methods: Ln the current study, we have investig ated the possibility that synthetic A beta(1-40) preferentially associ ates 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 bet ween apoE epsilon 3 and A beta(1-40) could not be disrupted by sodium dodecyl sulfate. In a parallel assay, no denaturant-resistant associat ion of A beta(1-40) with apoE epsilon 4 was detectable. Conclusions: T hese results support the notion that the apoE epsilon 4 isoform may fo ster beta-amyloidogenesis because apoE epsilon 4 is inefficient in for ming complexes with A beta.