Neuroinflammation drives APOE genotype-dependent differential expression of neprilysin

Journal of Neuroimmunology
David GraykowskiEiron Cudaback

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by the deposition of amyloid-beta (Aβ) plaques and widespread neuroinflammation. While the cause of AD remains unknown, multiple factors likely contribute to the disease, including heart disease, diabetes, previous head injury, as well as a number of genetic determinants. Inheritance of the apolipoprotein (APOE) ε4 allele represents the strongest genetic risk factor for development of AD, driving pathogenesis and increasing overall disease severity. APOE has long been recognized as a key regulator of cholesterol homeostasis, although a greater appreciation now exists for its role in various innate immune system processes. Indeed, APOE modulates inflammatory environments in brain in large part by altering gene expression profiles in glia, important mediators of immunity in the CNS. While the association between APOE and AD was first observed nearly three decades ago, the mechanism by which APOE ε4 influences the etiology and pathophysiology of AD is not well characterized. Overwhelming data supports the hypothesis that APOE ε4 dysregulates central amyloid metabolism by an undetermined molecular mechanism, thus laying the foundation for disease. A ...Continue Reading

Citations

Jul 3, 2021·Frontiers in Aging Neuroscience·Sanghamitra Bandyopadhyay

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