An ApoE-Abeta inhibition complex in Abeta fibril extension.
BACKGROUND
Literature reports differ dramatically in showing that apolipoprotein E either facilitates or inhibits Abeta aggregate formation in vitro. Resolution of the nature of the ApoE-Abeta interaction is critical for progress towards understanding its possible role in the modulation of Alzheimer's disease.


RESULTS
Here, we show that purified ApoE-Abeta co-aggregate is a poor seed of fibril formation. We also demonstrate ApoE inhibition of Abeta fibril growth in four independent aggregation assays, arguing that the poor fibril formation observed under these conditions is real and not an analytical artifact. We also directly show ApoE binding to immobilized Abeta fibrils by surface plasmon resonance.


CONCLUSIONS
The results suggest a unifying model in which ApoE binds to Abeta fibril seeds and nascent nuclei to generate stable complexes that inhibit the rapid extension of mono-component Abeta fibrils but at the same time can foster continued slow growth of mixed ApoE-Abeta aggregates. In vivo co-aggregate formation may be important in many examples of pathological protein misassembly.
Wood
S J
SJ
Macromolecular Sciences Department, SmithKline Beecham Pharmaceuticals, Inc., 709 Swedeland Road, King of Prussia, PA 19460, USA. wetzerlrb@voicenet.com
Chan
W
W
Wetzel
R
R
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D011994:Recombinant Proteins