TNF alpha plus IFN gamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs

The appearance of inflammatory markers associated with amyloid plaques indi cates a state of chronic inflammation in Alzheimer's disease (AD), Multiple epidemiological studies also suggest that patients taking anti-inflammator y drugs have a decreased risk of developing AD. Here we present evidence th at inflammatory cytokines can alter the metabolism of the beta-amyloid prec ursor protein (beta APP), We show that the combination of tumor necrosis fa ctor alpha and interferon gamma triggers the production of beta-amyloid pep tides and inhibits the secretion of soluble APPs by human neuronal and extr aneuronal cells. The results demonstrate a new mechanism by which inflammat ory components can exacerbate the fundamental pathology in AD.