An ApoE-Aβ inhibition complex in Aβ fibril extension Original Research Article

Background: Literature reports differ dramatically in showing that apolipoprotein E either facilitates or inhibits Aβ aggregate formation in vitro. Resolution of the nature of the ApoE-Aβ interaction is critical for progress towards understanding its possible role in the modulation of Alzheimerʹs disease. Results: Here, we show that purified ApoE-Aβ co-aggregate is a poor seed of fibril formation. We also demonstrate ApoE inhibition of Aβ 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 Aβ fibrils by surface plasmon resonance. Conclusions: The results suggest a unifying model in which ApoE binds to Aβ fibril seeds and nascent nuclei to generate stable complexes that inhibit the rapid extension of mono-component Aβ fibrils but at the same time can foster continued slow growth of mixed ApoE-Aβ aggregates. In vivo co-aggregate formation may be important in many examples of pathological protein misassembly.