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Innate immunity and Alzheimer's disease
Author(s) -
Affaneh Amira,
Lahey Matthew,
Langston Zachary,
Cudaback Eiron
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.659.13
Subject(s) - neuroinflammation , disease , microglia , apolipoprotein e , innate immune system , neuroscience , inflammation , alzheimer's disease , allele , immune system , immunology , biology , medicine , genetics , gene , pathology
Alzheimer's disease (AD) is a devastating neurodegenerative disorder set to become one of the greatest public health challenges in modern history. Attempts at disease intervention have thus far proven unsuccessful, and so the need for identification of novel therapeutic targets has never been greater. The association between exaggerated brain inflammation and AD strongly suggests that a more complete understanding of the mechanisms underlying dysfunctional immune activity may allow for novel target identification. The APOE gene is uniquely polymorphic in humans and differentially modulates innate immune activity in brain, with the ɛ4 allele representing the greatest known genetic risk factor for development of AD. However, while genetic association helps to identify risk, it does little to inform us about the molecular mechanisms that underlie disease. Amyloid (A) β, a pleiotropic neurotoxic pepetide, aggregates to form insoluble senile plaques and represents the pathologic hallmark of AD. Indeed, significant evidence supports dysfunctional clearance of Aβ in the etiology and/or pathophysiology of AD. Furthermore, Aβ is a potent inflammagen, promoting neuroinflammation through direct activation of both microglia and astrocytes. Here we present data supporting APOE genotype‐dependent differential expression of key glial targets associated with AD pathophysiology.