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 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).


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.
Zhou
Z
Z
Laboratory of Alzheimer Research, Cornell University Medical College, New York, NY 10021, USA.
Smith
J D
JD
Greengard
P
P
Gandy
S
S
D016229:Amyloid beta-Peptides / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40)