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

Leon M. Tai, Shipra Mehra, Varsha Shete, Steve Estus, G. William Rebeck, Guojun D Bu, Mary Jo Ladu

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2
JournalMolecular Neurodegeneration
Volume9
Issue number1
DOIs
StatePublished - Jan 4 2014

Fingerprint

Apolipoprotein E4
Apolipoproteins E
Alzheimer Disease
Apolipoprotein E3
Therapeutics
Amyloid
Lipoproteins
Protein Isoforms
Alleles

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Apolipoprotein E
  • Apolipoprotein E/amyloid beta complex
  • Lipidation
  • Lipoprotein
  • Oligomeric amyloid beta

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

Soluble apoE/Aβ complex : Mechanism and therapeutic target for APOE4-induced AD risk. / Tai, Leon M.; Mehra, Shipra; Shete, Varsha; Estus, Steve; Rebeck, G. William; Bu, Guojun D; Ladu, Mary Jo.

In: Molecular Neurodegeneration, Vol. 9, No. 1, 2, 04.01.2014.

Research output: Contribution to journalArticle

Tai, Leon M. ; Mehra, Shipra ; Shete, Varsha ; Estus, Steve ; Rebeck, G. William ; Bu, Guojun D ; Ladu, Mary Jo. / Soluble apoE/Aβ complex : Mechanism and therapeutic target for APOE4-induced AD risk. In: Molecular Neurodegeneration. 2014 ; Vol. 9, No. 1.
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