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Cited by 116Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Tai, Leon M, Mehra, Shipra, Shete, Varsha, Estus, Steve, Rebeck, G William, Bu, Guojun, LaDu, Mary Jo·2014·Molecular Neurodegeneration
DOI 10.1186/1750-1326-9-2PMC PMC3897976
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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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Authors
Tai, L. M., Mehra, S., Shete, V., Estus, S., Rebeck, G. W., Bu, G., & LaDu, M. J.
Affiliations
  • University of Illinois Chicago (US)
  • University of Kentucky (US)
  • Georgetown University (US)
  • Mayo Clinic (US)
Corresponding author
LaDu, Mary Jo
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2014-01-04
Volume
9
Issue
1
Pages
2-2
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-9-2
PMC
PMC3897976
OpenAlex
W2120831615
Cited by
116
References
115
Citations by year
2026: 5 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 10 · 2015: 15 · 2014: 12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
Funders
  • Alzheimer's Association (ZEN-08-899000, UL1RR029879)
  • National Institutes of Health
  • University of Illinois at Urbana-Champaign
  • National Institute on Aging (P01AG030128, R01AG027924, RF1AG046205, R01AG046205)
  • National Institute of Neurological Disorders and Stroke (P01NS074969)
  • National Center for Research Resources (UL1RR029879)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
apolipoprotein E, APOE ε4, amyloid-beta, soluble amyloid-beta oligomers, Alzheimer's disease risk, APOE isoforms, therapeutic target, neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Humans, Protein Binding, Risk Factors, Solubility, Amyloid beta-Peptides, Genetic Predisposition to Disease, Apolipoprotein E4

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