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01.12.2014 | Review | Ausgabe 1/2014 Open Access

Molecular Neurodegeneration 1/2014

Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk

Molecular Neurodegeneration > Ausgabe 1/2014
Leon M Tai, Shipra Mehra, Varsha Shete, Steve Estus, G William Rebeck, Guojun Bu, Mary Jo LaDu
Wichtige Hinweise

Competing interests

In collaboration with Skip Binder, MJL developed the antibody MOAB-2 used to develop the apoE/Aβ complex and oAβ ELISAs. MOAB-2 is licensed as a research tool to multiple companies. Also for research purposes, Biosensis Pty Ltd has licensed the rights to ELISA kits with MOAB-2 for oAβ and apoE/Aβ.

Authors’ contributions

LMT: Prepared the manuscript and Tables. SM: Provided input on, and preparation of, the Tables with LMT and MJL. VS: Provided significant input on final manuscript preparation, revision and submission. SE/GWR/GB: Collaborators who advised and provided significant input on the content and direction of the manuscript text. MJL: Provided fundamental contributions to the manuscript conception and preparation. All authors read and approved the final manuscript.


The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer’s disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we propose that compared to apoE3, apoE4-containing lipoproteins are less lipidated, leading to less stable apoE4/Aβ complexes, resulting in reduced apoE4/Aβ levels and increased accumulation, particularly of oAβ. Evidence that support or counter this argument, as well as the therapeutic significance of this pathway to neurodegeneration, are discussed.
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