{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:18:23Z","timestamp":1792498703765,"version":"4.5.0"},"reference-count":157,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001835","name":"Universiteit Maastricht","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001835","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The kynurenine pathway (KP) might be involved in pathophysiological processes associated with dementia, but clinical studies reported contradictory results. This systematic review and meta-analysis summarized the available evidence for (i) differences in KP metabolites in patients with cognitive impairment compared to cognitively healthy individuals and (ii) associations between KP metabolites and cognitive functioning. English, full-length articles with prospective, cross-sectional, or case\u2013control study designs, published in Pubmed, Embase, PsychINFO, or the Cochrane Database of Systematic Reviews up to October 2023, were included. Random-effects meta-analyses of standardized mean differences (SMD) were performed. Heterogeneity, meta-regression, small study bias, and study quality assessments were carried out. Of 8797 retrieved studies, 98 were eligible for the systematic review. Meta-analyses comparing Alzheimer\u2019s disease (AD) dementia patients to controls (n\u2009=\u200927 studies) indicated lower CSF levels of tryptophan (SMD\u2009= \u2212\u20090.26 [95% CI\u2009\u2212\u20090.41,\u2009\u2212\u20090.12]), 3-hydroxykynurenine (\u2212\u20090.21 [\u2212\u20090.39,\u2009\u2212\u20090.04]), anthranilic acid (\u2212\u20090.28 [\u2212\u20090.48,\u2009\u2212\u20090.08]), and quinolinic acid (\u2212\u20090.38 [\u2212\u20090.56,\u2009\u2212\u20090.21]) in AD dementia, while CSF levels of kynurenic acid were higher (0.18 [0.01, 0.35]). Blood levels of tryptophan (\u2212\u20090.39 [\u2212\u20090.51,\u2009\u2212\u20090.28]), kynurenic acid (\u2212\u20090.31 [\u2212\u20090.47,\u2009\u2212\u20090.15]), xanthurenic acid (\u2212\u20090.34 [\u2212\u20090.54,\u2009\u2212\u20090.15]), and 3-hydroxyanthranilic acid (\u2212\u20090.42 [\u2212\u20090.61,\u2009\u2212\u20090.22]) were lower in AD dementia. For some of these metabolites, similar directions were observed in meta-analyses comparing individuals with mild cognitive impairment with controls, although the number of included studies in these analyses was relatively small (n\u2009=\u200911). Associations with cognitive test scores were inconclusive and generally non-significant. These results suggest that AD dementia is associated with lower blood levels of several KP metabolites. Findings challenge current assumptions of neurotoxic quinolinic acid levels being associated with dementia.\u00a0<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11357-025-01636-3","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T02:07:35Z","timestamp":1746670055000},"page":"4585-4619","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Kynurenine pathway dysregulation in cognitive impairment and dementia: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"48","author":[{"given":"Kyonghwan","family":"Choe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieke","family":"Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L. A.","family":"van den Hove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone J. P. M.","family":"Eussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Kenis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez H. G. B.","family":"Ramakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans R. J.","family":"Verhey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P. F.","family":"Rutten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2398-0609","authenticated-orcid":false,"given":"Sebastian","family":"K\u00f6hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"issue":"5","key":"1636_CR1","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/S1474-4422(16)00062-4","volume":"15","author":"B Winblad","year":"2016","unstructured":"Winblad B, et al. Defeating Alzheimer\u2019s disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15(5):455\u2013532.","journal-title":"Lancet Neurol"},{"key":"1636_CR2","doi-asserted-by":"crossref","unstructured":"Association, A.s., 2018 Alzheimer\u2019s disease facts and figures. Alzheimers & Dementia, 2018; 14(3): p. 367\u2013425.","DOI":"10.1016\/j.jalz.2018.02.001"},{"key":"1636_CR3","volume-title":"Global status report on the public health response to dementia","author":"WH Organization","year":"2021","unstructured":"Organization WH. Global status report on the public health response to dementia. Geneva: World Health Organization; 2021."},{"key":"1636_CR4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.psychres.2018.08.041","volume":"269","author":"Y Wu","year":"2018","unstructured":"Wu Y, et al. Kynurenine pathway changes in late-life depression with memory deficit. Psychiatry Res. 2018;269:45\u20139.","journal-title":"Psychiatry Res"},{"key":"1636_CR5","doi-asserted-by":"crossref","unstructured":"Sorgdrager, F.J.H., et al., Age- and disease-specific changes of the kynurenine pathway in Parkinson\u2019s and Alzheimer\u2019s disease. Journal of Neurochemistry., 2019.","DOI":"10.1111\/jnc.14843"},{"issue":"2","key":"1636_CR6","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1111\/jnc.15360","volume":"158","author":"FB Rodrigues","year":"2021","unstructured":"Rodrigues FB, et al. Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington\u2019s disease. J Neurochem. 2021;158(2):539\u201353.","journal-title":"J Neurochem"},{"key":"1636_CR7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jpsychires.2021.05.004","volume":"139","author":"P Zhang","year":"2021","unstructured":"Zhang P, et al. Kynurenine metabolism and metabolic syndrome in patients with schizophrenia. J Psychiatr Res. 2021;139:54\u201361.","journal-title":"J Psychiatr Res"},{"key":"1636_CR8","first-page":"258","volume":"1","author":"M Seishima","year":"2021","unstructured":"Seishima M, et al. Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis. Exploration of Immunology. 2021;1:258\u201368.","journal-title":"Exploration of Immunology"},{"key":"1636_CR9","doi-asserted-by":"publisher","first-page":"1257159","DOI":"10.3389\/fimmu.2023.1257159","volume":"14","author":"AA Mangoni","year":"2023","unstructured":"Mangoni AA, Zinellu A. A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases. Front Immunol. 2023;14:1257159.","journal-title":"Front Immunol"},{"key":"1636_CR10","doi-asserted-by":"crossref","unstructured":"Biernacki, T., et al., Kynurenines in the pathogenesis of multiple sclerosis: therapeutic perspectives. Cells, 2020;9(6).","DOI":"10.3390\/cells9061564"},{"key":"1636_CR11","doi-asserted-by":"crossref","unstructured":"Gouasmi, R., et al., The kynurenine pathway and cancer: why keep it simple when you can make it complicated. Cancers (Basel), 2022;14(11).","DOI":"10.3390\/cancers14112793"},{"issue":"2","key":"1636_CR12","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41416-023-02245-7","volume":"129","author":"H-N Girithar","year":"2023","unstructured":"Girithar H-N, et al. Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials. Br J Cancer. 2023;129(2):185\u2013203.","journal-title":"Br J Cancer"},{"issue":"11","key":"1636_CR13","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1007\/s00125-021-05521-4","volume":"64","author":"L Bakker","year":"2021","unstructured":"Bakker L, et al. Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study. Diabetologia. 2021;64(11):2445\u201357.","journal-title":"Diabetologia"},{"key":"1636_CR14","doi-asserted-by":"publisher","first-page":"117864691769193","DOI":"10.1177\/1178646917691938","volume":"10","author":"AA Badawy","year":"2017","unstructured":"Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. 2017;10:1178646917691938.","journal-title":"Int J Tryptophan Res"},{"key":"1636_CR15","doi-asserted-by":"publisher","first-page":"646909","DOI":"10.1155\/2014\/646909","volume":"2014","author":"J Reyes Ocampo","year":"2014","unstructured":"Reyes Ocampo J, et al. Kynurenines with neuroactive and redox properties: relevance to aging and brain diseases. Oxid Med Cell Longev. 2014;2014: 646909.","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"1636_CR16","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s10534-005-4528-6","volume":"19","author":"K Murakami","year":"2006","unstructured":"Murakami K, Haneda M, Yoshino M. Prooxidant action of xanthurenic acid and quinoline compounds: role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2\u2019-deoxyguanosine in DNA. Biometals. 2006;19(4):429\u201335.","journal-title":"Biometals"},{"issue":"4","key":"1636_CR17","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3177\/jnsv.47.306","volume":"47","author":"K Murakami","year":"2001","unstructured":"Murakami K, Ito M, Yoshino M. Xanthurenic acid inhibits metal ion-induced lipid peroxidation and protects NADP-isocitrate dehydrogenase from oxidative inactivation. J Nutr Sci Vitaminol (Tokyo). 2001;47(4):306\u201310.","journal-title":"J Nutr Sci Vitaminol (Tokyo)"},{"issue":"1\u20133","key":"1636_CR18","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1385\/BTER:108:1-3:077","volume":"108","author":"T Hirai","year":"2005","unstructured":"Hirai T, et al. Effects of some naturally occurring iron ion chelators on in vitro superoxide radical formation. Biol Trace Elem Res. 2005;108(1\u20133):77\u201385.","journal-title":"Biol Trace Elem Res"},{"key":"1636_CR19","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4137\/IJTR.S4282","volume":"3","author":"LG Darlington","year":"2010","unstructured":"Darlington LG, et al. On the biological importance of the 3-hydroxyanthranilic acid: anthranilic acid ratio. Int J Tryptophan Res. 2010;3:51\u20139.","journal-title":"Int J Tryptophan Res"},{"issue":"2","key":"1636_CR20","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3233\/JAD-170929","volume":"62","author":"D Z\u00e1dori","year":"2018","unstructured":"Z\u00e1dori D, et al. Alzheimer\u2019s disease: recent concepts on the relation of mitochondrial disturbances, excitotoxicity, neuroinflammation, and kynurenines. J Alzheimers Dis. 2018;62(2):523\u201347.","journal-title":"J Alzheimers Dis"},{"issue":"2","key":"1636_CR21","doi-asserted-by":"publisher","first-page":"495","DOI":"10.3233\/JAD-170485","volume":"60","author":"LM Giil","year":"2017","unstructured":"Giil LM, et al. Kynurenine pathway metabolites in Alzheimer\u2019s disease. J Alzheimers Dis. 2017;60(2):495\u2013504.","journal-title":"J Alzheimers Dis"},{"key":"1636_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2019.03.015","volume":"80","author":"KR Jacobs","year":"2019","unstructured":"Jacobs KR, et al. Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer\u2019s disease and relationship to amyloid-\u03b2 and tau. Neurobiol Aging. 2019;80:11\u201320.","journal-title":"Neurobiol Aging"},{"issue":"1","key":"1636_CR23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13195-020-00741-z","volume":"13","author":"L Whiley","year":"2021","unstructured":"Whiley L, et al. Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer\u2019s disease. Alzheimers Res Ther. 2021;13(1):20.","journal-title":"Alzheimers Res Ther"},{"key":"1636_CR24","doi-asserted-by":"crossref","unstructured":"Willette, A.A., et al., Inflammation, negative affect, and amyloid burden in Alzheimer\u2019s disease: insights from the kynurenine pathway. Brain Behav Immun, 2021.","DOI":"10.1016\/j.bbi.2021.03.019"},{"key":"1636_CR25","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-S\u00e1nchez, M., et al., Kynurenic acid levels are increased in the CSF of Alzheimer\u2019s disease patients. Biomolecules, 2020;10(4).","DOI":"10.3390\/biom10040571"},{"issue":"1","key":"1636_CR26","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13195-019-0551-7","volume":"11","author":"V van der Velpen","year":"2019","unstructured":"van der Velpen V, et al. Systemic and central nervous system metabolic alterations in Alzheimer\u2019s disease. Alzheimers Res Ther. 2019;11(1):93.","journal-title":"Alzheimers Res Ther"},{"key":"1636_CR27","doi-asserted-by":"publisher","first-page":"997240","DOI":"10.3389\/fimmu.2022.997240","volume":"13","author":"M Fathi","year":"2022","unstructured":"Fathi M, et al. Dynamic changes in metabolites of the kynurenine pathway in Alzheimer\u2019s disease, Parkinson\u2019s disease, and Huntington\u2019s disease: a systematic review and meta-analysis. Front Immunol. 2022;13: 997240.","journal-title":"Front Immunol"},{"issue":"4","key":"1636_CR28","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.3233\/JAD-220295","volume":"88","author":"AF Almulla","year":"2022","unstructured":"Almulla AF, et al. The tryptophan catabolite or kynurenine pathway in Alzheimer\u2019s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2022;88(4):1325\u201339.","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"1636_CR29","first-page":"286","volume":"45","author":"BS Fernandes","year":"2023","unstructured":"Fernandes BS, et al. The kynurenine pathway in Alzheimer\u2019s disease: a meta-analysis of central and peripheral levels. Braz J Psychiatry. 2023;45(3):286\u201397.","journal-title":"Braz J Psychiatry"},{"key":"1636_CR30","doi-asserted-by":"publisher","first-page":"n160","DOI":"10.1136\/bmj.n160","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372: n160.","journal-title":"BMJ"},{"key":"1636_CR31","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.","journal-title":"BMJ"},{"key":"1636_CR32","doi-asserted-by":"crossref","unstructured":"Wohlin, C. Guidelines for snowballing in systematic literature studies and a replication in software engineering. in Proceedings of the 18th international conference on evaluation and assessment in software engineering. 2014.","DOI":"10.1145\/2601248.2601268"},{"key":"1636_CR33","unstructured":"GA Wells, B.S., D O\u2019Connell, J Peterson, V Welch, M Losos, P Tugwell, The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000."},{"issue":"6","key":"1636_CR34","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.cardfail.2017.04.007","volume":"23","author":"JA Cannon","year":"2017","unstructured":"Cannon JA, et al. Cognitive impairment and heart failure: systematic review and meta-analysis. J Card Fail. 2017;23(6):464\u201375.","journal-title":"J Card Fail"},{"key":"1636_CR35","unstructured":"Cohen, J., Statistical power analysis for the behavioral sciences. 2nd edition ed. 1988: Lawrence Erlbaum Associates."},{"issue":"11","key":"1636_CR36","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","volume":"21","author":"JP Higgins","year":"2002","unstructured":"Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539\u201358.","journal-title":"Stat Med"},{"issue":"7414","key":"1636_CR37","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins JP, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557\u201360.","journal-title":"BMJ"},{"issue":"3","key":"1636_CR38","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S0304-3959(99)00302-4","volume":"85","author":"DJ Gavaghan","year":"2000","unstructured":"Gavaghan DJ, Moore AR, McQuay HJ. An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain. 2000;85(3):415\u201324.","journal-title":"Pain"},{"key":"1636_CR39","unstructured":"Higgins JPT, T.J., Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane handbook for systematic reviews of interventions version 6.2 (updated February 2021). 2021; Available from: www.training.cochrane.org\/handbook."},{"issue":"7109","key":"1636_CR40","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","volume":"315","author":"M Egger","year":"1997","unstructured":"Egger M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629\u201334.","journal-title":"BMJ"},{"key":"1636_CR41","doi-asserted-by":"publisher","first-page":"117864691987788","DOI":"10.1177\/1178646919877883","volume":"12","author":"SE Hafstad Solvang","year":"2019","unstructured":"Hafstad Solvang SE, et al. Kynurenines, neuropsychiatric symptoms, and cognitive prognosis in patients with mild dementia. Int J Tryptophan Res. 2019;12:1178646919877883.","journal-title":"Int J Tryptophan Res"},{"key":"1636_CR42","doi-asserted-by":"crossref","unstructured":"McCann, A., et al., Serum tyrosine is associated with better cognition in Lewy body dementia. Brain Research, 2021;1765.","DOI":"10.1016\/j.brainres.2021.147481"},{"issue":"3","key":"1636_CR43","first-page":"147","volume":"22","author":"F Mashige","year":"1993","unstructured":"Mashige F, et al. Development of a high-performance liquid chromatography system with multi- electrode electrochemical detectors for determination of levels of neurotransmitters in cerebrospinal fluid. Japanese Journal of Clinical Chemistry. 1993;22(3):147\u201355.","journal-title":"Japanese Journal of Clinical Chemistry"},{"issue":"4","key":"1636_CR44","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1159\/000287953","volume":"7","author":"E Kaiser","year":"2010","unstructured":"Kaiser E, et al. Cerebrospinal fluid concentrations of functionally important amino acids and metabolic compounds in patients with mild cognitive impairment and Alzheimer\u2019s disease. Neurodegener Dis. 2010;7(4):251\u20139.","journal-title":"Neurodegener Dis"},{"issue":"12","key":"1636_CR45","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.jalz.2017.04.009","volume":"13","author":"V Chouraki","year":"2017","unstructured":"Chouraki V, et al. Association of amine biomarkers with incident dementia and Alzheimer\u2019s disease in the Framingham Study. Alzheimer\u2019s and Dementia. 2017;13(12):1327\u201336.","journal-title":"Alzheimer\u2019s and Dementia"},{"issue":"9","key":"1636_CR46","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.jalz.2017.01.020","volume":"13","author":"JB Toledo","year":"2017","unstructured":"Toledo JB, et al. Metabolic network failures in Alzheimer\u2019s disease: a biochemical road map. Alzheimer\u2019s and Dementia. 2017;13(9):965\u201384.","journal-title":"Alzheimer\u2019s and Dementia"},{"key":"1636_CR47","doi-asserted-by":"crossref","unstructured":"Nho, K., et al., Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression. Brain Commun, 2021. 3(3): p. fcab139.","DOI":"10.1093\/braincomms\/fcab139"},{"key":"1636_CR48","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neurobiolaging.2019.10.014","volume":"86","author":"Z Huo","year":"2020","unstructured":"Huo Z, et al. Brain and blood metabolome for Alzheimer\u2019s dementia: findings from a targeted metabolomics analysis. Neurobiol Aging. 2020;86:123\u201333.","journal-title":"Neurobiol Aging"},{"key":"1636_CR49","doi-asserted-by":"publisher","first-page":"105783","DOI":"10.1016\/j.nbd.2022.105783","volume":"171","author":"M Cespedes","year":"2022","unstructured":"Cespedes M, et al. Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-beta. Neurobiol Dis. 2022;171: 105783.","journal-title":"Neurobiol Dis"},{"key":"1636_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120819","volume":"454","author":"L Bakker","year":"2023","unstructured":"Bakker L, et al. The role of the kynurenine pathway in cognitive functioning after stroke: a prospective clinical study. J Neurol Sci. 2023;454: 120819.","journal-title":"J Neurol Sci"},{"key":"1636_CR51","doi-asserted-by":"crossref","unstructured":"Knapskog, A.B., et al., Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer\u2019s disease. Alzheimer\u2019s and Dementia, 2023.","DOI":"10.1002\/alz.13162"},{"key":"1636_CR52","doi-asserted-by":"crossref","unstructured":"Aquilani, R., et al., Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation. Frontiers in Aging Neuroscience, 2023. 15.","DOI":"10.3389\/fnagi.2023.1237469"},{"key":"1636_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4137\/IJTR.S13958","volume":"7","author":"M Wennstrom","year":"2014","unstructured":"Wennstrom M, et al. Kynurenic acid levels in cerebrospinal fluid from patients with Alzheimer\u2019s disease or dementia with lewy bodies. Int J Tryptophan Res. 2014;7:1\u20137.","journal-title":"Int J Tryptophan Res"},{"key":"1636_CR54","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.chroma.2013.06.005","volume":"1302","author":"C Ib\u00e1\u00f1ez","year":"2013","unstructured":"Ib\u00e1\u00f1ez C, et al. A new metabolomic workflow for early detection of Alzheimer\u2019s disease. J Chromatogr A. 2013;1302:65\u201371.","journal-title":"J Chromatogr A"},{"key":"1636_CR55","doi-asserted-by":"crossref","unstructured":"Kaddurah-Daouk, R., et al., Alterations in metabolic pathways and networks in Alzheimer\u2019s disease. Translational Psychiatry, 2013;3 (no pagination).","DOI":"10.1038\/tp.2013.18"},{"issue":"5","key":"1636_CR56","doi-asserted-by":"publisher","first-page":"e63644","DOI":"10.1371\/journal.pone.0063644","volume":"8","author":"E Trushina","year":"2013","unstructured":"Trushina E, et al. Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer\u2019s disease using metabolomics. PLoS ONE. 2013;8(5): e63644.","journal-title":"PLoS ONE"},{"issue":"2","key":"1636_CR57","doi-asserted-by":"publisher","first-page":"e31501","DOI":"10.1371\/journal.pone.0031501","volume":"7","author":"C Czech","year":"2012","unstructured":"Czech C, et al. Metabolite profiling of Alzheimer\u2019s disease cerebrospinal fluid. PLoS ONE. 2012;7(2): e31501.","journal-title":"PLoS ONE"},{"issue":"3","key":"1636_CR58","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.jalz.2010.06.001","volume":"7","author":"R Kaddurah-Daouk","year":"2011","unstructured":"Kaddurah-Daouk R, et al. Metabolomic changes in autopsy-confirmed Alzheimer\u2019s disease. Alzheimer\u2019s and Dementia. 2011;7(3):309\u201317.","journal-title":"Alzheimer\u2019s and Dementia"},{"issue":"2","key":"1636_CR59","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s00726-006-0409-8","volume":"32","author":"AN Fonteh","year":"2007","unstructured":"Fonteh AN, et al. Free amino acid and dipeptide changes in the body fluids from Alzheimer\u2019s disease subjects. Amino Acids. 2007;32(2):213\u201324.","journal-title":"Amino Acids"},{"issue":"2","key":"1636_CR60","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s007020050149","volume":"106","author":"H Baran","year":"1999","unstructured":"Baran H, Jellinger K, Deecke L. Kynurenine metabolism in Alzheimer\u2019s disease. J Neural Transm. 1999;106(2):165\u201381.","journal-title":"J Neural Transm"},{"issue":"2\u20133","key":"1636_CR61","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s007020050057","volume":"105","author":"JA Molina","year":"1998","unstructured":"Molina JA, et al. Cerebrospinal fluid levels of non-neurotransmitter amino acids in patients with Alzheimer\u2019s disease. J Neural Transm (Vienna). 1998;105(2\u20133):279\u201386.","journal-title":"J Neural Transm (Vienna)"},{"issue":"2\u20133","key":"1636_CR62","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/BF02259654","volume":"9","author":"H Tohgi","year":"1995","unstructured":"Tohgi H, et al. Indoleamine concentrations in cerebrospinal fluid from patients with Alzheimer type and Binswanger type dementias before and after administration of citalopram, a synthetic serotonin uptake inhibitor. Journal of Neural Transmission - Parkinson\u2019s Disease and Dementia Section. 1995;9(2\u20133):121\u201331.","journal-title":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section"},{"issue":"Pt 5","key":"1636_CR63","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1093\/brain\/115.5.1249","volume":"115","author":"MP Heyes","year":"1992","unstructured":"Heyes MP, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain. 1992;115(Pt 5):1249\u201373.","journal-title":"Brain"},{"issue":"1","key":"1636_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF02252617","volume":"6","author":"M Martinez","year":"1993","unstructured":"Martinez M, et al. Amino acid concentrations in cerebrospinal fluid and serum in Alzheimer\u2019s disease and vascular dementia. J Neural Transm Park Dis Dement Sect. 1993;6(1):1\u20139.","journal-title":"J Neural Transm Park Dis Dement Sect"},{"issue":"1","key":"1636_CR65","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0304-3940(92)90322-X","volume":"141","author":"H Tohgi","year":"1992","unstructured":"Tohgi H, et al. Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. Neurosci Lett. 1992;141(1):9\u201312.","journal-title":"Neurosci Lett"},{"issue":"4","key":"1636_CR66","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1111\/j.1471-4159.1990.tb03143.x","volume":"55","author":"MF Beal","year":"1990","unstructured":"Beal MF, et al. Kynurenine pathway measurements in Huntington\u2019s disease striatum: evidence for reduced formation of kynurenic acid. J Neurochem. 1990;55(4):1327\u201339.","journal-title":"J Neurochem"},{"issue":"1\u20132","key":"1636_CR67","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/0304-3940(89)90043-8","volume":"105","author":"MM Mourdian","year":"1989","unstructured":"Mourdian MM, et al. No changes in central quinolinic acid levels in Alzheimer\u2019s disease. Neurosci Lett. 1989;105(1\u20132):233\u20138.","journal-title":"Neurosci Lett"},{"issue":"5","key":"1636_CR68","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s11064-020-03002-5","volume":"45","author":"J Janssens","year":"2020","unstructured":"Janssens J, et al. Monoaminergic and kynurenergic characterization of frontotemporal dementia and amyotrophic lateral sclerosis in cerebrospinal fluid and serum. Neurochem Res. 2020;45(5):1191\u2013201.","journal-title":"Neurochem Res"},{"key":"1636_CR69","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.bbi.2023.04.015","volume":"111","author":"L Bakker","year":"2023","unstructured":"Bakker L, et al. Correlations between kynurenines in plasma and CSF, and their relation to markers of Alzheimer\u2019s disease pathology. Brain Behav Immun. 2023;111:312\u20139.","journal-title":"Brain Behav Immun"},{"key":"1636_CR70","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.dadm.2017.07.006","volume":"8","author":"FA de Leeuw","year":"2017","unstructured":"de Leeuw FA, et al. Blood-based metabolic signatures in Alzheimer\u2019s disease. Alzheimers Dement (Amst). 2017;8:196\u2013207.","journal-title":"Alzheimers Dement (Amst)"},{"issue":"4","key":"1636_CR71","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00406-012-0384-x","volume":"263","author":"MJ Schwarz","year":"2013","unstructured":"Schwarz MJ, et al. Increased 3-Hydroxykynurenine serum concentrations differentiate Alzheimer\u2019s disease patients from controls. Eur Arch Psychiatry Clin Neurosci. 2013;263(4):345\u201352.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1636_CR72","doi-asserted-by":"crossref","unstructured":"Xu, J., et al., Sex-specific metabolic pathways were associated with Alzheimer\u2019s disease (AD) endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort. Biomedicines, 2021. 9(11).","DOI":"10.3390\/biomedicines9111610"},{"key":"1636_CR73","doi-asserted-by":"crossref","unstructured":"Klatt, S., et al., A six-metabolite panel as potential blood-based biomarkers for Parkinson\u2019s disease. npj Parkinson's Disease, 2021;7(1).","DOI":"10.1038\/s41531-021-00239-x"},{"issue":"1","key":"1636_CR74","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3233\/JAD-230142","volume":"94","author":"M Liu","year":"2023","unstructured":"Liu M, et al. Chiral amino acid profiling in serum reveals potential biomarkers for Alzheimer\u2019s disease. Journal of Alzheimer\u2019s Disease. 2023;94(1):291\u2013301.","journal-title":"Journal of Alzheimer\u2019s Disease"},{"issue":"3","key":"1636_CR75","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/acn3.726","volume":"6","author":"CN Lin","year":"2019","unstructured":"Lin CN, et al. A metabolomic approach to identifying biomarkers in blood of Alzheimer\u2019s disease. Ann Clin Transl Neurol. 2019;6(3):537\u201345.","journal-title":"Ann Clin Transl Neurol"},{"key":"1636_CR76","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.biopha.2017.03.101","volume":"90","author":"P Atukeren","year":"2017","unstructured":"Atukeren P, et al. The efficacy of donepezil administration on acetylcholinesterase activity and altered redox homeostasis in Alzheimer\u2019s disease. Biomed Pharmacother. 2017;90:786\u201395.","journal-title":"Biomed Pharmacother"},{"key":"1636_CR77","doi-asserted-by":"crossref","unstructured":"Oxenkrug, G., et al., Peripheral tryptophan - kynurenine metabolism associated with metabolic syndrome is different in Parkinson\u2019s and Alzheimer\u2019s diseases. Endocrinol Diabetes Metab J, 2017;1(4).","DOI":"10.31038\/EDMJ.2017141"},{"key":"1636_CR78","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jpba.2014.10.010","volume":"107","author":"R Gonzalez-Dominguez","year":"2015","unstructured":"Gonzalez-Dominguez R, Garcia-Barrera T, Gomez-Ariza JL. Metabolite profiling for the identification of altered metabolic pathways in Alzheimer\u2019s disease. J Pharm Biomed Anal. 2015;107:75\u201381.","journal-title":"J Pharm Biomed Anal"},{"key":"1636_CR79","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.talanta.2014.07.075","volume":"131","author":"R Gonz\u00e1lez-Dom\u00ednguez","year":"2015","unstructured":"Gonz\u00e1lez-Dom\u00ednguez R, Garc\u00eda-Barrera T, G\u00f3mez-Ariza JL. Application of a novel metabolomic approach based on atmospheric pressure photoionization mass spectrometry using flow injection analysis for the study of Alzheimer\u2019s disease. Talanta. 2015;131:480\u20139.","journal-title":"Talanta"},{"key":"1636_CR80","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jpba.2014.05.023","volume":"98","author":"R Gonzalez-Dominguez","year":"2014","unstructured":"Gonzalez-Dominguez R, Garcia-Barrera T, Gomez-Ariza JL. Metabolomic study of lipids in serum for biomarker discovery in Alzheimer\u2019s disease using direct infusion mass spectrometry. J Pharm Biomed Anal. 2014;98:321\u20136.","journal-title":"J Pharm Biomed Anal"},{"issue":"2","key":"1636_CR81","doi-asserted-by":"publisher","first-page":"204","DOI":"10.2478\/v10039-010-0023-6","volume":"55","author":"E Gulaj","year":"2010","unstructured":"Gulaj E, et al. Kynurenine and its metabolites in Alzheimer\u2019s disease patients. Adv Med Sci. 2010;55(2):204\u201311.","journal-title":"Adv Med Sci"},{"issue":"2","key":"1636_CR82","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.neuint.2006.08.012","volume":"50","author":"Z Hartai","year":"2007","unstructured":"Hartai Z, et al. Decreased serum and red blood cell kynurenic acid levels in Alzheimer\u2019s disease. Neurochem Int. 2007;50(2):308\u201313.","journal-title":"Neurochem Int"},{"issue":"3","key":"1636_CR83","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s007020050029","volume":"107","author":"B Widner","year":"2000","unstructured":"Widner B, et al. Tryptophan degradation and immune activation in Alzheimer\u2019s disease. J Neural Transm. 2000;107(3):343\u201353.","journal-title":"J Neural Transm"},{"key":"1636_CR84","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-1-4615-4709-9_19","volume":"467","author":"B Widner","year":"1999","unstructured":"Widner B, et al. Degradation of tryptophan in neurodegenerative disorders. Adv Exp Med Biol. 1999;467:133\u20138.","journal-title":"Adv Exp Med Biol"},{"issue":"4","key":"1636_CR85","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/BF03339794","volume":"10","author":"S Bonaccorso","year":"1998","unstructured":"Bonaccorso S, et al. Serotonin-immune interactions in elderly volunteers and in patients with Alzheimer\u2019s disease (DAT): Lower plasma tryptophan availability to the brain in the elderly and increased serum interleukin-6 in DAT. Aging - Clinical and Experimental Research. 1998;10(4):316\u201323.","journal-title":"Aging - Clinical and Experimental Research"},{"issue":"2\u20133","key":"1636_CR86","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s007020050058","volume":"105","author":"D Fekkes","year":"1998","unstructured":"Fekkes D, et al. Abnormal amino acid metabolism in patients with early stage Alzheimer dementia. J Neural Transm (Vienna). 1998;105(2\u20133):287\u201394.","journal-title":"J Neural Transm (Vienna)"},{"issue":"4","key":"1636_CR87","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/BF02252924","volume":"2","author":"H Basun","year":"1990","unstructured":"Basun H, et al. Amino acid concentrations in cerebrospinal fluid and plasma in Alzheimer\u2019s disease and healthy control subjects. J Neural Transm Park Dis Dement Sect. 1990;2(4):295\u2013304.","journal-title":"J Neural Transm Park Dis Dement Sect"},{"issue":"2","key":"1636_CR88","first-page":"159","volume":"33","author":"SE Watkins","year":"1989","unstructured":"Watkins SE, et al. Plasma amino acids in patients with senile dementia and in subjects with Down\u2019s syndrome at an age vulnerable to Alzheimer changes. J Ment Defic Res. 1989;33(2):159\u201366.","journal-title":"J Ment Defic Res"},{"issue":"12","key":"1636_CR89","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.clinbiochem.2010.04.072","volume":"43","author":"NJ Li","year":"2010","unstructured":"Li NJ, et al. Plasma metabolic profiling of Alzheimer\u2019s disease by liquid chromatography\/mass spectrometry. Clin Biochem. 2010;43(12):992\u20137.","journal-title":"Clin Biochem"},{"issue":"6","key":"1636_CR90","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.14336\/AD.2020.0217","volume":"11","author":"Y Shao","year":"2020","unstructured":"Shao Y, et al. Alteration of metabolic profile and potential biomarkers in the plasma of Alzheimer\u2019s disease. Aging Dis. 2020;11(6):1459\u201370.","journal-title":"Aging Dis"},{"issue":"19","key":"1636_CR91","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1002\/elps.201300019","volume":"34","author":"M Tsuruoka","year":"2013","unstructured":"Tsuruoka M, et al. Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum and saliva from neurodegenerative dementia patients. Electrophoresis. 2013;34(19):2865\u201372.","journal-title":"Electrophoresis"},{"key":"1636_CR92","doi-asserted-by":"publisher","first-page":"113424","DOI":"10.1016\/j.jpba.2020.113424","volume":"189","author":"ALM Santos","year":"2020","unstructured":"Santos ALM, et al. Frontotemporal dementia: plasma metabolomic signature using gas chromatography-mass spectrometry. J Pharm Biomed Anal. 2020;189: 113424.","journal-title":"J Pharm Biomed Anal"},{"key":"1636_CR93","doi-asserted-by":"crossref","unstructured":"Teruya, T., et al., Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites. Proceedings of the National Academy of Sciences of the United States of America, 2021;118(37).","DOI":"10.1073\/pnas.2022857118"},{"issue":"3","key":"1636_CR94","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1093\/ajcn\/49.3.559","volume":"49","author":"D Rudman","year":"1989","unstructured":"Rudman D, et al. Fasting plasma amino acids in elderly men. Am J Clin Nutr. 1989;49(3):559\u201366.","journal-title":"Am J Clin Nutr"},{"issue":"2","key":"1636_CR95","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1017\/S0033291700009119","volume":"16","author":"DE Thomas","year":"1986","unstructured":"Thomas DE, et al. Tryptophan and nutritional status of patients with senile dementia. Psychol Med. 1986;16(2):297\u2013305.","journal-title":"Psychol Med"},{"key":"1636_CR96","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1192\/bjp.139.6.580","volume":"139","author":"DM Shaw","year":"1981","unstructured":"Shaw DM, et al. Pilot study of amino acids in senile dementia. Br J Psychiatry. 1981;139:580\u20132.","journal-title":"Br J Psychiatry"},{"issue":"3\u20134","key":"1636_CR97","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1159\/000441565","volume":"16","author":"PS Rommer","year":"2016","unstructured":"Rommer PS, et al. Lowered levels of carbonyl proteins after vitamin B supplementation in patients with mild cognitive impairment and Alzheimer\u2019s disease. Neurodegener Dis. 2016;16(3\u20134):284\u20139.","journal-title":"Neurodegener Dis"},{"issue":"9\u201310","key":"1636_CR98","first-page":"441","volume":"56","author":"J Greilberger","year":"2010","unstructured":"Greilberger J, et al. Carbonyl proteins as a clinical marker in Alzheimer\u2019s disease and its relation to tryptophan degradation and immune activation. Clin Lab. 2010;56(9\u201310):441\u20138.","journal-title":"Clin Lab"},{"key":"1636_CR99","doi-asserted-by":"crossref","unstructured":"Ikeuchi, T., et al., Development of a novel nutrition-related multivariate biomarker for mild cognitive impairment based on the plasma free amino acid profile. Nutrients, 2022;14(3).","DOI":"10.3390\/nu14030637"},{"key":"1636_CR100","doi-asserted-by":"crossref","unstructured":"Ramos-Chavez, L.A., et al., Low serum tryptophan levels as an indicator of global cognitive performance in nondemented women over 50 years of age. Oxidative Medicine and Cellular Longevity, 2018;2018 (no pagination).","DOI":"10.1155\/2018\/8604718"},{"key":"1636_CR101","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.cca.2019.10.023","volume":"500","author":"C Pe\u00f1a-Bautista","year":"2020","unstructured":"Pe\u00f1a-Bautista C, et al. Plasma alterations in cholinergic and serotonergic systems in early Alzheimer disease: diagnosis utility. Clin Chim Acta. 2020;500:233\u201340.","journal-title":"Clin Chim Acta"},{"issue":"1","key":"1636_CR102","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13024-020-00421-4","volume":"16","author":"A Cogo","year":"2021","unstructured":"Cogo A, et al. Increased serum QUIN\/KYNA is a reliable biomarker of post-stroke cognitive decline. Mol Neurodegener. 2021;16(1):7.","journal-title":"Mol Neurodegener"},{"issue":"12","key":"1636_CR103","doi-asserted-by":"publisher","first-page":"3287","DOI":"10.1039\/C5MB00470E","volume":"11","author":"M Liu","year":"2015","unstructured":"Liu M, et al. Potential of serum metabolites for diagnosing post-stroke cognitive impairment. Mol BioSyst. 2015;11(12):3287\u201396.","journal-title":"Mol BioSyst"},{"issue":"1\u20133","key":"1636_CR104","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0304-3940(89)90709-X","volume":"100","author":"GB Baker","year":"1989","unstructured":"Baker GB, Reynolds GP. Biogenic amines and their metabolites in Alzheimer\u2019s disease: noradrenaline, 5-hydroxytryptamine and 5-hydroxyindole-3-acetic acid depleted in hippocampus but not in substantia innominata. Neurosci Lett. 1989;100(1\u20133):335\u20139.","journal-title":"Neurosci Lett"},{"issue":"1","key":"1636_CR105","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0304-3940(95)12256-7","volume":"203","author":"D Storga","year":"1996","unstructured":"Storga D, et al. Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients. Neurosci Lett. 1996;203(1):29\u201332.","journal-title":"Neurosci Lett"},{"issue":"6","key":"1636_CR106","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/0168-0102(85)90020-3","volume":"2","author":"H Arai","year":"1985","unstructured":"Arai H, et al. Free amino acids in post-mortem cerebral cortices from patients with Alzheimer-type dementia. Neurosci Res. 1985;2(6):486\u201390.","journal-title":"Neurosci Res"},{"issue":"4","key":"1636_CR107","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/0197-4580(84)90009-5","volume":"5","author":"H Arai","year":"1984","unstructured":"Arai H, et al. A preliminary study of free amino acids in the postmortem temporal cortex from Alzheimer-type dementia patients. Neurobiol Aging. 1984;5(4):319\u201321.","journal-title":"Neurobiol Aging"},{"issue":"2","key":"1636_CR108","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1021\/acs.jproteome.5b01020","volume":"15","author":"G Paglia","year":"2016","unstructured":"Paglia G, et al. Unbiased metabolomic investigation of Alzheimer\u2019s disease brain points to dysregulation of mitochondrial aspartate metabolism. J Proteome Res. 2016;15(2):608\u201318.","journal-title":"J Proteome Res"},{"issue":"5","key":"1636_CR109","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/j.1471-4159.1980.tb07883.x","volume":"35","author":"I Tarbit","year":"1980","unstructured":"Tarbit I, et al. Hippocampal free amino acids in Alzheimer\u2019s disease. J Neurochem. 1980;35(5):1246\u20139.","journal-title":"J Neurochem"},{"issue":"6","key":"1636_CR110","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.bbadis.2016.03.001","volume":"1862","author":"J Xu","year":"2016","unstructured":"Xu J, et al. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer\u2019s disease: snapshot of a pervasive metabolic disorder. Biochim Biophys Acta. 2016;1862(6):1084\u201392.","journal-title":"Biochim Biophys Acta"},{"key":"1636_CR111","doi-asserted-by":"crossref","unstructured":"Heylen, A., et al., Brain kynurenine pathway metabolite levels may reflect extent of neuroinflammation in ALS, FTD and early onset AD. Pharmaceuticals, 2023;16(4).","DOI":"10.3390\/ph16040615"},{"issue":"79","key":"1636_CR112","doi-asserted-by":"publisher","first-page":"75499","DOI":"10.1039\/C6RA16802G","volume":"6","author":"Q Liang","year":"2016","unstructured":"Liang Q, et al. High-throughput metabolomics analysis discovers salivary biomarkers for predicting mild cognitive impairment and Alzheimer\u2019s disease. RSC Adv. 2016;6(79):75499\u2013504.","journal-title":"RSC Adv"},{"key":"1636_CR113","doi-asserted-by":"crossref","unstructured":"Yilmaz, A., et al., Targeted metabolic profiling of urine highlights a potential biomarker panel for the diagnosis of Alzheimer\u2019s disease and mild cognitive impairment: a pilot study. Metabolites, 2020;10(9).","DOI":"10.3390\/metabo10090357"},{"key":"1636_CR114","doi-asserted-by":"crossref","unstructured":"Nik Mohd Fakhruddin, N.N.I., et al., Urine untargeted metabolomic profiling is associated with the dietary pattern of successful aging among Malaysian elderly. Nutrients, 2020;12(10).","DOI":"10.3390\/nu12102900"},{"key":"1636_CR115","doi-asserted-by":"crossref","unstructured":"Wu, L., et al., Altered gut microbial metabolites in amnestic mild cognitive impairment and Alzheimer\u2019s disease: signals in host-microbe interplay. Nutrients, 2021;13(1).","DOI":"10.3390\/nu13010228"},{"key":"1636_CR116","doi-asserted-by":"crossref","unstructured":"Gold, A.B., et al., The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment. Journal of Neuroinflammation, 2011;8 (no pagination).","DOI":"10.1186\/1742-2094-8-17"},{"issue":"10","key":"1636_CR117","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1515\/CCLM.1998.132","volume":"36","author":"F Leblhuber","year":"1998","unstructured":"Leblhuber F, et al. Activated immune system in patients with Huntington\u2019s disease. Clin Chem Lab Med. 1998;36(10):747\u201350.","journal-title":"Clin Chem Lab Med"},{"key":"1636_CR118","doi-asserted-by":"crossref","unstructured":"Solvang, S.E.H., et al., The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study. Brain, Behavior, and Immunity, 2019;75: p. 155\u2013162.","DOI":"10.1016\/j.bbi.2018.10.003"},{"issue":"1\u20132","key":"1636_CR119","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jns.2013.03.007","volume":"329","author":"P Wissmann","year":"2013","unstructured":"Wissmann P, et al. Immune activation in patients with Alzheimer\u2019s disease is associated with high serum phenylalanine concentrations. J Neurol Sci. 2013;329(1\u20132):29\u201333.","journal-title":"J Neurol Sci"},{"key":"1636_CR120","doi-asserted-by":"crossref","unstructured":"Park, S.A., et al., Metabolite profiling revealed that a gardening activity program improves cognitive ability correlated with BDNF levels and serotonin metabolism in the elderly. Int J Environ Res Public Health, 2020. 17(2).","DOI":"10.3390\/ijerph17020541"},{"key":"1636_CR121","doi-asserted-by":"crossref","unstructured":"Chatterjee, P., et al., Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults. J Neurochem, 2020.","DOI":"10.1111\/jnc.15128"},{"issue":"3","key":"1636_CR122","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.3233\/JAD-170447","volume":"59","author":"OC Kuster","year":"2017","unstructured":"Kuster OC, et al. Novel blood-based biomarkers of cognition, stress, and physical or cognitive training in older adults at risk of dementia: preliminary evidence for a role of BDNF, irisin, and the kynurenine pathway. Journal of Alzheimer\u2019s Disease. 2017;59(3):1097\u2013111.","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"1636_CR123","doi-asserted-by":"crossref","unstructured":"Vints, W.A.J., et al., Inflammatory blood biomarker kynurenine is linked with elevated neuroinflammation and neurodegeneration in older adults: evidence from two 1H-MRS post-processing analysis methods. Frontiers in Psychiatry, 2022;13.","DOI":"10.3389\/fpsyt.2022.859772"},{"key":"1636_CR124","doi-asserted-by":"crossref","unstructured":"Huang, J., et al., Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia. Translational Psychiatry, 2021;11(1).","DOI":"10.1038\/s41398-021-01311-z"},{"issue":"3","key":"1636_CR125","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3233\/JAD-220906","volume":"91","author":"DC Parker","year":"2023","unstructured":"Parker DC, et al. Tryptophan metabolism and neurodegeneration: longitudinal associations of kynurenine pathway metabolites with cognitive performance and plasma Alzheimer\u2019s disease and related dementias biomarkers in the Duke Physical Performance Across the LifeSpan Study. J Alzheimers Dis. 2023;91(3):1141\u201350.","journal-title":"J Alzheimers Dis"},{"issue":"11","key":"1636_CR126","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1038\/s41380-019-0401-9","volume":"25","author":"J Kindler","year":"2020","unstructured":"Kindler J, et al. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2020;25(11):2860\u201372.","journal-title":"Mol Psychiatry"},{"key":"1636_CR127","doi-asserted-by":"crossref","unstructured":"Anderson, E.W., et al., Quinolinic acid, a kynurenine\/tryptophan pathway metabolite, associates with impaired cognitive test performance in systemic lupus erythematosus. Lupus Science and Medicine, 2021;8(1).","DOI":"10.1136\/lupus-2021-000559"},{"key":"1636_CR128","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.psyneuen.2017.04.015","volume":"81","author":"M Platzer","year":"2017","unstructured":"Platzer M, et al. Tryptophan breakdown and cognition in bipolar disorder. Psychoneuroendocrinology. 2017;81:144\u201350.","journal-title":"Psychoneuroendocrinology"},{"issue":"3","key":"1636_CR129","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1159\/000520152","volume":"81","author":"K Hebbrecht","year":"2022","unstructured":"Hebbrecht K, et al. The role of kynurenines in cognitive dysfunction in bipolar disorder. Neuropsychobiology. 2022;81(3):184\u201391.","journal-title":"Neuropsychobiology"},{"key":"1636_CR130","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4137\/IJTR.S2097","volume":"2","author":"Y Chen","year":"2009","unstructured":"Chen Y, Guillemin GJ. Kynurenine pathway metabolites in humans: disease and healthy States. Int J Tryptophan Res. 2009;2:1\u201319.","journal-title":"Int J Tryptophan Res"},{"issue":"4","key":"1636_CR131","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/0014-2999(81)90587-2","volume":"72","author":"TW Stone","year":"1981","unstructured":"Stone TW, Perkins MN. Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Eur J Pharmacol. 1981;72(4):411\u20132.","journal-title":"Eur J Pharmacol"},{"key":"1636_CR132","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3389\/fimmu.2018.01363","volume":"9","author":"L Bo","year":"2018","unstructured":"Bo L, Guojun T, Li G. An expanded neuroimmunomodulation axis: sCD83-indoleamine 2,3-dioxygenase-kynurenine pathway and updates of kynurenine pathway in neurologic diseases. Front Immunol. 2018;9:1363.","journal-title":"Front Immunol"},{"issue":"8","key":"1636_CR133","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1111\/j.1582-4934.2010.01123.x","volume":"14","author":"ZT Kincses","year":"2010","unstructured":"Kincses ZT, Toldi J, Vecsei L. Kynurenines, neurodegeneration and Alzheimer\u2019s disease. J Cell Mol Med. 2010;14(8):2045\u201354.","journal-title":"J Cell Mol Med"},{"issue":"10","key":"1636_CR134","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1080\/14728222.2018.1524877","volume":"22","author":"R Sharma","year":"2018","unstructured":"Sharma R, et al. Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer\u2019s disease. Expert Opin Ther Targets. 2018;22(10):849\u201367.","journal-title":"Expert Opin Ther Targets"},{"issue":"4","key":"1636_CR135","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1365-2990.2005.00655.x","volume":"31","author":"GJ Guillemin","year":"2005","unstructured":"Guillemin GJ, et al. Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer\u2019s disease hippocampus. Neuropathol Appl Neurobiol. 2005;31(4):395\u2013404.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1636_CR136","first-page":"S200","volume":"54","author":"GJ Guillemin","year":"2005","unstructured":"Guillemin GJ, et al. Mass spectroscopic detection of quinolinic acid in microdissected Alzheimer\u2019s disease plaques. Inflamm Res. 2005;54:S200\u2013S200.","journal-title":"Inflamm Res"},{"issue":"7","key":"1636_CR137","doi-asserted-by":"publisher","first-page":"e6344","DOI":"10.1371\/journal.pone.0006344","volume":"4","author":"A Rahman","year":"2009","unstructured":"Rahman A, et al. The excitotoxin quinolinic acid induces tau phosphorylation in human neurons. PLoS ONE. 2009;4(7): e6344.","journal-title":"PLoS ONE"},{"issue":"18","key":"1636_CR138","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1097\/00001756-200312190-00005","volume":"14","author":"GJ Guillemin","year":"2003","unstructured":"Guillemin GJ, et al. A beta 1\u201342 induces production of quinolinic acid by human macrophages and microglia. NeuroReport. 2003;14(18):2311\u20135.","journal-title":"NeuroReport"},{"key":"1636_CR139","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/978-1-4615-0135-0_19","volume":"527","author":"GJ Guillemin","year":"2003","unstructured":"Guillemin GJ, et al. Quinolinic acid in the pathogenesis of Alzheimer\u2019s disease. Adv Exp Med Biol. 2003;527:167\u201376.","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"1636_CR140","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/BF01739651","volume":"239","author":"E Sofic","year":"1989","unstructured":"Sofic E, et al. Brain quinolinic acid in Alzheimer\u2019s dementia. Eur Arch Psychiatry Neurol Sci. 1989;239(3):177\u20139.","journal-title":"Eur Arch Psychiatry Neurol Sci"},{"issue":"1","key":"1636_CR141","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nrd3793","volume":"12","author":"L Vecsei","year":"2013","unstructured":"Vecsei L, et al. Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov. 2013;12(1):64\u201382.","journal-title":"Nat Rev Drug Discov"},{"issue":"21","key":"1636_CR142","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1016\/0024-3205(96)00173-7","volume":"58","author":"H Baran","year":"1996","unstructured":"Baran H, et al. Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with Down syndrome. Life Sci. 1996;58(21):1891\u20139.","journal-title":"Life Sci"},{"issue":"1","key":"1636_CR143","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/0022-510X(92)90191-M","volume":"108","author":"MF Beal","year":"1992","unstructured":"Beal MF, et al. Kynurenic acid concentrations are reduced in Huntington\u2019s disease cerebral cortex. J Neurol Sci. 1992;108(1):80\u20137.","journal-title":"J Neurol Sci"},{"issue":"6","key":"1636_CR144","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.cell.2011.05.020","volume":"145","author":"D Zwilling","year":"2011","unstructured":"Zwilling D, et al. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell. 2011;145(6):863\u201374.","journal-title":"Cell"},{"issue":"2","key":"1636_CR145","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.bbr.2010.02.041","volume":"210","author":"P Carrillo-Mora","year":"2010","unstructured":"Carrillo-Mora P, et al. Protective effect of systemic L-kynurenine and probenecid administration on behavioural and morphological alterations induced by toxic soluble amyloid beta (25\u201335) in rat hippocampus. Behav Brain Res. 2010;210(2):240\u201350.","journal-title":"Behav Brain Res"},{"issue":"1\u20133","key":"1636_CR146","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.ejphar.2011.05.069","volume":"667","author":"L Gellert","year":"2011","unstructured":"Gellert L, et al. Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia. Eur J Pharmacol. 2011;667(1\u20133):182\u20137.","journal-title":"Eur J Pharmacol"},{"issue":"17\u201318","key":"1636_CR147","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.lfs.2008.02.014","volume":"82","author":"H Robotka","year":"2008","unstructured":"Robotka H, et al. Neuroprotection achieved in the ischaemic rat cortex with L-kynurenine sulphate. Life Sci. 2008;82(17\u201318):915\u20139.","journal-title":"Life Sci"},{"issue":"7","key":"1636_CR148","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrn3257","volume":"13","author":"R Schwarcz","year":"2012","unstructured":"Schwarcz R, et al. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13(7):465\u201377.>","journal-title":"Nat Rev Neurosci"},{"key":"1636_CR149","doi-asserted-by":"publisher","first-page":"154148","DOI":"10.1016\/j.cyto.2017.09.004","volume":"122","author":"R Baumgartner","year":"2019","unstructured":"Baumgartner R, Forteza MJ, Ketelhuth DFJ. The interplay between cytokines and the kynurenine pathway in inflammation and atherosclerosis. Cytokine. 2019;122: 154148.","journal-title":"Cytokine"},{"issue":"1","key":"1636_CR150","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.biopha.2009.07.002","volume":"64","author":"OK Bitzer-Quintero","year":"2010","unstructured":"Bitzer-Quintero OK, et al. Antioxidant activity of tryptophan in rats under experimental endotoxic shock. Biomed Pharmacother. 2010;64(1):77\u201381.","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"1636_CR151","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1515\/pteridines.2002.13.4.140","volume":"13","author":"G Weiss","year":"2002","unstructured":"Weiss G, et al. Tryptophan metabolites as scavengers of reactive oxygen and chlorine species. Pteridines. 2002;13(4):140\u20133.","journal-title":"Pteridines"},{"issue":"26","key":"1636_CR152","doi-asserted-by":"publisher","first-page":"10215","DOI":"10.1021\/jf062134n","volume":"54","author":"M Pazos","year":"2006","unstructured":"Pazos M, Andersen ML, Skibsted LH. Amino acid and protein scavenging of radicals generated by iron\/hydroperoxide system: an electron spin resonance spin trapping study. J Agric Food Chem. 2006;54(26):10215\u201321.","journal-title":"J Agric Food Chem"},{"issue":"4","key":"1636_CR153","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1515\/tjb-2020-0150","volume":"46","author":"A Unlu","year":"2021","unstructured":"Unlu A, et al. HPLC and LC-MS\/MS measurement methods for the quantification of asymmetric dimethylarginine (ADMA) and related metabolites. Turkish Journal of Biochemistry. 2021;46(4):327\u201347.","journal-title":"Turkish Journal of Biochemistry"},{"issue":"2","key":"1636_CR154","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/S0014-827X(00)00006-9","volume":"55","author":"ME Abdel-Hamid","year":"2000","unstructured":"Abdel-Hamid ME. Comparative LC\u2013MS and HPLC analyses of selected antiepileptics and beta-blocking drugs. Il Farmaco. 2000;55(2):136\u201345.","journal-title":"Il Farmaco"},{"issue":"8","key":"1636_CR155","doi-asserted-by":"publisher","first-page":"e0135437","DOI":"10.1371\/journal.pone.0135437","volume":"10","author":"M Carayol","year":"2015","unstructured":"Carayol M, et al. Reliability of serum metabolites over a two-year period: a targeted metabolomic approach in fasting and non-fasting samples from EPIC. PLoS ONE. 2015;10(8):e0135437\u2013e0135437.","journal-title":"PLoS ONE"},{"issue":"1","key":"1636_CR156","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s13195-024-01623-4","volume":"16","author":"K Choe","year":"2024","unstructured":"Choe K, et al. Alzheimer\u2019s disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway. Alzheimers Res Ther. 2024;16(1):259.","journal-title":"Alzheimers Res Ther"},{"issue":"3","key":"1636_CR157","doi-asserted-by":"publisher","first-page":"e0119452","DOI":"10.1371\/journal.pone.0119452","volume":"10","author":"SF Graham","year":"2015","unstructured":"Graham SF, et al. Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer\u2019s disease. PLoS ONE. 2015;10(3): e0119452.","journal-title":"PLoS ONE"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01636-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-025-01636-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01636-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:02:00Z","timestamp":1783771320000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-025-01636-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":157,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["1636"],"URL":"https:\/\/doi.org\/10.1007\/s11357-025-01636-3","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,8]]},"assertion":[{"value":"10 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.\u00a0","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}