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Open Access 01-12-2014 | Review

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

Authors: Leon M Tai, Shipra Mehra, Varsha Shete, Steve Estus, G William Rebeck, Guojun Bu, Mary Jo LaDu

Published in: Molecular Neurodegeneration | Issue 1/2014

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.

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Title: Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk
Authors: Leon M Tai
Shipra Mehra
Varsha Shete
Steve Estus
G William Rebeck
Guojun Bu
Mary Jo LaDu
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2014
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-9-2

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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