ArticleJournal of Alzheimer's disease : JAD2023
Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Kynurenine pathway dysregulation in cognitive impairment and dementia: a systematic review and meta-analysis.GeroScience · 2026Pooled it
- Epilepsy as a Disorder of Neuroimmune Metabolism: The Kynurenine Pathway as a Link Between Cognitive and Psychiatric Dysfunction.Biomolecules · 2026Review
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Tryptophan Metabolism in Digestive and Extra-Digestive Diseases: Mechanisms, Clinical Implications, and Therapeutic Perspectives.Nutrients · 2026Review
- Review
- Article
- Assessment of Kynurenine Pathway Enzyme Activity in Ocular Diseases: Associations with Cataract, Diabetes, Glaucoma, and Pseudoexfoliation Syndrome.Journal of clinical medicine · 2025Article
- The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study.BMC rheumatology · 2025Article
- Kynurenine pathway: a possible new mechanism for exercise in the prevention and treatment of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- The Microbiota-Gut-Brain Axis and Neurological Disorders: A Comprehensive Review.Life (Basel, Switzerland) · 2024Review
- From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment.International journal of molecular sciences · 2024Review
- Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2024Article
- Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach.Scientific reports · 2023Article
- Early-onset Alzheimer's disease with depression as the first symptom: a case report with literature review.Frontiers in psychiatry · 2023Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundThe kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD).
objectiveThe objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study.
methodsThe Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7).
resultsOver two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers.
conclusionOur findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.
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