The kynurenine pathway in Alzheimer's disease: a meta-analysis of central and peripheral levels.

Autor: Fernandes BS; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Inam ME; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Enduru N; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA., Quevedo J; Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Zhao Z; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA. Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA. Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) [Braz J Psychiatry] 2023 May-Jun; Vol. 45 (3), pp. 286-297. Date of Electronic Publication: 2022 Feb 08.
DOI: 10.47626/1516-4446-2022-2962
Abstrakt: Objective: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer's disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD.
Methods: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood.
Results: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral blood. The kynurenine-to-tryptophan ratio was only increased in peripheral blood of the AD group. 3-Hydroxykynurenine was decreased only in cerebrospinal fluid and showed higher variability in the CN group than the AD group. Kynurenic acid was increased in cerebrospinal fluid and decreased in peripheral blood. Finally, there were no changes in kynurenine and quinolinic acid between the groups.
Conclusions: Our results suggested a shift toward the kynurenine pathway in both the brain and in the periphery, as well as a shift towards increased kynurenic acid production in the brain but decreased production in peripheral blood. In addition, our analysis indicated dissociation between the central and peripheral levels, as well as between plasma and serum for some of these metabolites. Finally, changes in the kynurenine pathway are suggested to be a core component of AD. More studies are warranted to verify and consolidate our results.
Competing Interests: JQ has conducted clinical research at LivaNova and Janssen, has been a speaker for Myriad Neuroscience and AbbVie, has equity at the Instituto de Neurociencias Dr. Joao Quevedo, and receives book royalties from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. The other authors report no conflicts of interest.
Databáze: MEDLINE
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