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The tryptophan catabolite or kynurenine pathway in Alzheimer's disease: a systematic review and meta-analysis.

Background: Alzheimer's disease (AD), characterized by gradual brain dysfunction and memory loss, is one of the major elderly health issues worldwide. Neuroinflammation and increased oxidative stress contribute to the pathophysiology of AD, thereby presumably inducing tryptophan (TRP) degradation through the TRP catabolite (TRYCAT) pathway. Objectives: To delineate the activity of the TRYCAT pathway along with levels of TRP and tryptophan catabolites (TRYCATs) in AD patients. Methods: We employed PubMed, Google Scholar, Web of Science, and SciFinder to obtain the relevant articles through a search process lasting the entire February 2022. We found 19 eligible articles which involved 738 patients and 665 healthy controls. Results: Our result revealed a significant difference (p = 0.008) in the kynurenine (KYN)/TRP ratio (standardized mean difference, SMD = 0.216, 95% confidence interval, CI: 0.057; 0.376), and a significant decrease in TRP in AD patients (SMD = -0.520, 95% CI: -0.738; -0.302, p < 0.0001). Moreover, we also found a significant increase in the central nervous system (CNS, brain and cerebrospinal fluid, CSF) kynurenic acid (KA)/KYN ratio but not in peripheral blood, as well as a significant decrease in plasma KA and xanthurenic acid (XA) in the CNS and blood. Conclusions: AD is characterized by TRP depletion but not by an overactivity of the TRYCAT pathway. IDO-induced production of neurotoxic TRYCATs is not a key factor in the pathophysiology of AD.