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 Aβ1-42 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, Aβ1-40 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.
1Centre for Immunology, St. Vincent's Hospital, Darlinghurst, NSW 2010
4Departments of Neurology, St Vincent's Hospital, Darlinghurst, NSW 2010
2The Ray Williams Biomedical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia
3Department of Molecular Biochemistry, Central Research Institute, School of Medicine, Hokkaido University, Sapporo, Japan
CACorresponding Author: email@example.com
Received 10 August 2003; accepted 22 August 2003