Abstract
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.
Document Type
Article
Publication Date
1-4-2014
Digital Object Identifier (DOI)
http://dx.doi.org/10.1186/1750-1326-9-2
Repository Citation
Tai, Leon M.; Mehra, Shipra; Shete, Varsha; Estus, Steven; Rebeck, G. William; Bu, Guojun; and LaDu, Mary Jo, "Soluble apoE/Aβ Complex: Mechanism and Therapeutic target for APOE4-induced AD Risk" (2014). Sanders-Brown Center on Aging Faculty Publications. 29.
https://uknowledge.uky.edu/sbcoa_facpub/29
Notes/Citation Information
Published in Molecular Neurodegeneration, v. 9, no. 2, p. 1-14.
© 2014 Tai et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver applies to the data made available in this article, unless otherwise stated.