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

Molecular Neurodegeneration

Mary Jo LaDu²  Guojun Bu³  G William Rebeck¹  Steve Estus⁴  Varsha Shete²  Shipra Mehra²  Leon M Tai² 

[1] Department of Neuroscience, Georgetown University, Washington, DC 20057, USA;Department of Anatomy and Cell Biology, University of Illinois at Chicago, 808 S. Wood St., M/C 512, Chicago, IL 60612, USA;Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA;Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA

关键词: Lipidation;    Lipoprotein;    Oligomeric amyloid beta;    Apolipoprotein E/amyloid beta complex;    Apolipoprotein E;    Amyloid beta;    Alzheimer’s disease;   

Others  :  861894
DOI  :  10.1186/1750-1326-9-2

 received in 2013-11-28, accepted in 2013-12-27,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Tai et al.; licensee BioMed Central Ltd.

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