Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism

Ncurointlammation has been observed in association with neurodegenerative diseases including Alzheimer's disease (AD). In particular, a positive correlation has been documented between neuroinflammatory cytokine release and the progression of the AD, which suggests these cytokines are involved in AD pathophysiology. A histological hallmark of the AD is the presence of beta-amyloid (A beta) plaques and tau neurofibrillary tangles. Beta-amyloid is generated by the sequential cleavage of beta (beta) and gamma (gamma) sites in the amyloid precursor protein (APP) by beta- and gamma-secretase enzymes and its accumulation can result from either a decreased A beta clearance or increased metabolism of APR Previous studies reported that neuroinflammatory cytokines reduce the efflux transport of A beta, leading to elevated A beta concentrations in the brain. However, less is known about the effects of neuroinflammatory mediators on APP expression and metabolism. In this article, we review the modulatory role of neuroinflammatory cytokines on APP expression and metabolism, including their effects on beta- and gamma-secretase enzymes.