APOE ‐modulated Aβ‐induced neuroinflammation in Alzheimer's disease: current landscape, novel data, and future perspective
Year: 2015
Type: editorial
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. In this editorial review, we present data supporting the hypothesis that impaired apoE4 function modulates Aβ-induced effects on inflammatory receptor signaling, including amplification of detrimental (TLR4-p38α) and suppression of beneficial (IL-4R-nuclear receptor) pathways, resulting in an adverse NIP that causes neuronal dysfunction. NIP, Neuroinflammatory phenotype; P.I., pro-inflammatory; A.I., anti-inflammatory.
Source: Journal of Neurochemistry
DOI: 10.1111/jnc.13072
Authors: 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
Institutions: University of Illinois Chicago, University of Kentucky
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,330
Funders: Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of Illinois at Urbana-Champaign, University of Illinois at Chicago, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Office of the Vice Chancellor for Research, University of Illinois at Chicago
OpenAlex ID: W2019786269