APOE-modulated Aβ-induced neuroinflammation in Alzheimer's disease: Current landscape, novel data, and future perspective

Leon M. Tai, Shivesh Ghura, Kevin P. Koster, Vaiva Liakaite, Mark Maienschein-Cline, Pinal Kanabar, Nicole Collins, Manel Ben-Aissa, Arden Zhengdeng Lei, Neil Bahroos, Stefan J. Green, Bill Hendrickson, Linda J. Van Eldik, Mary Jo LaDu

Research output: Contribution to journalReview articlepeer-review

120 Scopus citations

Abstract

Chronic glial activation and neuroinflammation induced by the amyloid-β peptide (Aβ) contribute to Alzheimer's disease (AD) pathology. APOE4 is the greatest AD-genetic risk factor; increasing risk up to 12-fold compared to APOE3, with APOE4-specific neuroinflammation an important component of this risk. This editorial review discusses the role of APOE in inflammation and AD, via a literature review, presentation of novel data on Aβ-induced neuroinflammation, and discussion of future research directions. The complexity of chronic neuroinflammation, including multiple detrimental and beneficial effects occurring in a temporal and cell-specific manner, has resulted in conflicting functional data for virtually every inflammatory mediator. Defining a neuroinflammatory phenotype (NIP) is one way to address this issue, focusing on profiling the changes in inflammatory mediator expression during disease progression. Although many studies have shown that APOE4 induces a detrimental NIP in peripheral inflammation and Aβ-independent neuroinflammation, data for APOE-modulated Aβ-induced neuroinflammation are surprisingly limited. We present data supporting the hypothesis that impaired apoE4 function modulates Aβ-induced effects on inflammatory receptor signaling, including amplification of detrimental (toll-like receptor 4-p38α) and suppression of beneficial (IL-4R-nuclear receptor) pathways. To ultimately develop APOE genotype-specific therapeutics, it is critical that future studies define the dynamic NIP profile and pathways that underlie APOE-modulated chronic neuroinflammation.

Original languageEnglish
Pages (from-to)465-488
Number of pages24
JournalJournal of Neurochemistry
Volume133
Issue number4
DOIs
StatePublished - Mar 18 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Keywords

  • Alzheimer's disease
  • amyloid-β
  • apolipoprotein E
  • interleukin-4 receptor
  • neuroinflammation
  • toll-like receptor 4

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'APOE-modulated Aβ-induced neuroinflammation in Alzheimer's disease: Current landscape, novel data, and future perspective'. Together they form a unique fingerprint.

Cite this