Kynurenine pathway metabolite alterations in Down syndrome and Alzheimer's disease

Author(s)

dos Reis, Rafaela Gomes ; Singulani, Monique Patricio ; Forlenza, Orestes Vicente ; Gattaz, Wagner Farid ; Talib, Leda Leme

• Document type: Journal article
• Source: ALZHEIMERS & DEMENTIA; v. 21, n. 5, p. 7-pg., 2025-05-01.

Abstract

INTRODUCTION: Down syndrome (DS) is a genetic disorder that leads to intellectual disability and accelerated aging, increasing the risk of Alzheimer's disease (AD). 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. METHODS: A cross-sectional study was conducted involving DS, AD, and healthy participants. Plasma levels of tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, and quinolinic acid were analyzed by Liquid Chromatography coupled with Tandem Mass spectrometry (LC-MS/MS) methodology. RESULTS: Elevated kynurenine and other neuroprotective metabolites were found in DS individuals without cognitive decline, while significant differences in neurotoxic metabolites were observed between groups. DISCUSSION: Our findings suggest a link between kynurenine pathway dysregulation and cognitive decline, indicating alterations in DS and AD. (AU)

• FAPESP's process: 21/06378-1 - Analysis of the involvement of lithium in mitochondrial markers in Alzheimer's Disease
• Grantee: Monique Patricio Singulani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50873-3 - INCT 2014: National Institute of Biomarkers in Neuropsychiatry
• Grantee: Wagner Farid Gattaz
• Support Opportunities: Research Projects - Thematic Grants