{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:50:17Z","timestamp":1788385817772,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer Research Foundation Belgium","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"Alzheimer Research Foundation Belgium","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]},{"name":"Medical Research Foundation Antwerp","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"Medical Research Foundation Antwerp","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]},{"name":"Thomas Riellaerts research fund","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"Thomas Riellaerts research fund","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]},{"name":"Neurosearch Antwerp","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"Neurosearch Antwerp","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]},{"DOI":"10.13039\/501100010969","name":"Alzheimer Nederland","doi-asserted-by":"publisher","award":["20180027"],"award-info":[{"award-number":["20180027"]}],"id":[{"id":"10.13039\/501100010969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010969","name":"Alzheimer Nederland","doi-asserted-by":"publisher","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}],"id":[{"id":"10.13039\/501100010969","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Antwerp","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"University of Antwerp","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]},{"name":"Alzheimer Center of the University Medical Center Groningen","award":["20180027"],"award-info":[{"award-number":["20180027"]}]},{"name":"Alzheimer Center of the University Medical Center Groningen","award":["WE.03-2019-11"],"award-info":[{"award-number":["WE.03-2019-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: Despite distinct clinical profiles, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients share a remarkable portion of pathological features, with a substantial percentage of patients displaying a mixed disease phenotype. Kynurenine metabolism seems to play a role in dementia-associated neuroinflammation and has been linked to both diseases. We aimed to explore dissimilarities in kynurenine pathway metabolites in these early onset neurodegenerative disorders in a brain-region-specific manner. Methods: Using liquid chromatography mass spectrometry (LC-MS\/MS), kynurenine metabolite levels were determined in the brain samples of 98 healthy control subjects (n = 20) and patients with early onset Alzheimer\u2019s disease (EOAD) (n = 23), ALS (n = 20), FTD (n = 24) or a mixed FTD\u2013ALS (n = 11) disease profile. Results: Overall, the kynurenine pathway metabolite levels were significantly lower in patients with ALS compared to FTD, EOAD and control subjects in the frontal cortex, substantia nigra, hippocampus and neostriatum. Anthranilic acid levels and kynurenine-to-tryptophan ratios were consistently lower in all investigated brain regions in ALS compared to the other diagnostic groups. Conclusions: These results suggest that the contribution of kynurenine metabolism in neuroinflammation is lower in ALS than in FTD or EOAD and may also be traced back to differences in the age of onset between these disorders. Further research is necessary to confirm the potential of the kynurenine system as a therapeutic target in these early onset neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ph16040615","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Brain Kynurenine Pathway Metabolite Levels May Reflect Extent of Neuroinflammation in ALS, FTD and Early Onset AD"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2660-8984","authenticated-orcid":false,"given":"Annelies","family":"Heylen","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-5326","authenticated-orcid":false,"given":"Yannick","family":"Vermeiren","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health, Chair Group of Nutritional Biology, Wageningen University and Research, 6708 Wageningen, The Netherlands"},{"name":"Faculty of Medicine & Health Sciences, Translational Neurosciences, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido P.","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van Faassen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"van der Ley","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-6076","authenticated-orcid":false,"given":"Debby","family":"Van Dam","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center Groningen, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-2964","authenticated-orcid":false,"given":"Peter P.","family":"De Deyn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center Groningen, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2174\/1745017901309010088","article-title":"Epidemiology of early-onset dementia: A review of the literature","volume":"9","author":"Vieira","year":"2013","journal-title":"Clin. 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