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

Figure 1

Schematic diagram for the effects of neuroinflammatory cytokines on amyloid precursor protein (APP) processing and beta-amyloid (Aβ) production. Amyloid precursor proteins (APP) are cleaved by beta (β) and gamma (γ) sites in the APP by β- and γ-secretase enzymes producing Aβ in the brain. (a) Normal levels and activity of APP, APP metabolic enzymes, and neuroinflammatory cytokines in control brain. (b) In Alzheimer disease (AD), Aβ is accumulated in the brain leading to formation of Aβ oligomers. This effect leads to activation of microglia, which increases the production of neuroinflammatory cytokines. These cytokines increase APP levels, upregulate β-secretase and γ-secretase, and decrease Aβ clearance in the brain. These effects result in further increase in Aβ concentrations and formation of Aβ oligomers and plaques.

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