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The pathophysiology of AD and DS is multifactorial, involving amyloid precursor protein overexpression, neuroinflammation, and oxidative stress. This study investigates kynurenine pathway metabolites in elderly individuals with DS (with\/without cognitive decline), AD, and cognitively healthy controls to clarify their roles in these pathogeneses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A cross\u2010sectional study was conducted involving DS, AD, and healthy participants. Plasma levels of tryptophan, kynurenine, 3\u2010hydroxykynurenine, anthranilic acid, 3\u2010hydroxyanthranilic acid, and quinolinic acid were analyzed by Liquid Chromatography coupled with Tandem Mass spectrometry (LC\u2010MS\/MS) methodology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Elevated kynurenine and other neuroprotective metabolites were found in DS individuals without cognitive decline, while significant differences in neurotoxic metabolites were observed between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings suggest a link between kynurenine pathway dysregulation and cognitive decline, indicating alterations in DS and AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>There are altered kynurenine pathway metabolites in Down syndrome and Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Elevated neuroprotective metabolites are found in Down syndrome without cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Significant differences in neurotoxic metabolites among study groups were analyzed.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>There is a potential link between kynurenine pathway dysregulation and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The study provides insights into metabolic changes in aging and neurodegeneration.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70197","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T23:18:22Z","timestamp":1747869502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Kynurenine pathway metabolite alterations in Down syndrome and Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Rafaela Gomes","family":"dos Reis","sequence":"first","affiliation":[{"name":"Laboratory of Neuroscience (LIM\u201027) Departamento e Instituto de Psiquiatria Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN) Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique Patricio","family":"Singulani","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience (LIM\u201027) Departamento e Instituto de Psiquiatria Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN) Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Centro de Neuroci\u00eancias Translacionais (CNT) Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orestes Vicente","family":"Forlenza","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience (LIM\u201027) Departamento e Instituto de Psiquiatria Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN) Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Centro de Neuroci\u00eancias Translacionais (CNT) Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner Farid","family":"Gattaz","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience (LIM\u201027) Departamento e Instituto de Psiquiatria Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Instituto 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Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70197","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70197","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:29:28Z","timestamp":1789558168000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/alz.70197"],"URL":"https:\/\/doi.org\/10.1002\/alz.70197","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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