title: TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs.
abstract: The appearance of inflammatory markers associated with amyloid plaques indicates a state of chronic inflammation in Alzheimer's disease (AD). Multiple epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. Here we present evidence that inflammatory cytokines can alter the metabolism of the beta-amyloid precursor protein (betaAPP). We show that the combination of tumor necrosis factor alpha and interferon gamma triggers the production of beta-amyloid peptides and inhibits the secretion of soluble APPs by human neuronal and extraneuronal cells. The results demonstrate a new mechanism by which inflammatory components can exacerbate the fundamental pathology in AD.
authors.affiliation: a Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Blasko
authors.forename: F
authors.initials: F
authors.lastname: Marx
authors.forename: E
authors.initials: E
authors.lastname: Steiner
authors.forename: T
authors.initials: T
authors.lastname: Hartmann
authors.forename: B
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma