Year: 2014
Type: editorial
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.
Source: Molecular Neurodegeneration
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: ApoE Receptor Biology and Neurodegeneration, G2625822199, ApoE pathway in cerebrovascular Aβ clearance in Alzheimer's disease, G3934755009, Center for Clinical and Translational Science, ApoE isoform-specific therapy for Alzheimer disease, ApoE isoform-specific therapy for Alzheimer disease, Regional, Synaptic, Cellular Modulation of Abeta Metabolism
OpenAlex ID: W2120831615