IDO level increase in Kynurenine Pathway Contributes to the Development of Alzheimer's Disease

Tryptophan is crucial to many functions of the body. Research has shown that its involvement in the Kynurenine pathway (KP) also plays a role in the development of various neurodegenerative diseases (ND). As one of the upstream enzymes in KP, Indoleamine 2,3-dioxygenase (IDO) controls the production of several critical downstream metabolites. Some of these metabolites, such as kynurenic acid (KYNA), possess neuroprotective properties, while some other, such as quinolinic acid (QUIN) are neurotoxic. Hence, the balance between these species is closely linked to the pathogenesis of NDs. Interesting, a positive association has also been found between the level of IDO and the level of amyloid peptide Aβ1-42 involved in Alzheimer's disease. Therefore, this experiment aims to investigate the mechanistic link between increases in levels of IDO and beta-amyloid production. We hypothesize that an increase in IDO level caused by systemic inflammation promotes the generation of key markers of AD by causing an imbalance in levels of tryptophan metabolites, specifically by shifting towards production of neurotoxic metabolite (QUIN) over neuroprotective species (KYNA).