title: A beta 1-42 induces production of quinolinic acid by human macrophages and microglia.
abstract: We hypothesized that the tryptophan catabolites produced through the kynurenine pathway (KP), and more particularly the excitotoxin quinolinic acid (QUIN), may play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we demonstrated that aggregated amyloid peptide A beta 1-42 induced indoleamine 2,3-dioxygenase (IDO) expression and resulted in a significant increase in production of QUIN by human primary macrophages and microglia. In contrast, A beta 1-40 and prion peptide (PrP) 106-126 did not induce any significant increase in QUIN production. These data imply that local QUIN production may be one of the factors involved in the pathogenesis of neuronal damage in AD.
authors.affiliation: Centre for Immunology, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia. g.guillemin@cfl.unsw.edu.au
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: George A
authors.initials: GA
authors.lastname: Smythe
authors.forename: Laura A
authors.initials: LA
authors.lastname: Veas
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured; D005333:Fetus; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D017378:Quinolinic Acid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D017378:Quinolinic Acid