Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Kynurenine pathway metabolite alterations in Down syndrome and Alzheimer's disease.
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Dos Reis Rafaela Gomes, Singulani Monique Patricio, Forlenza Orestes Vicente, Gattaz Wagner Farid, Talib Leda Leme
Аннотация
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.
HIGHLIGHTS: There are altered kynurenine pathway metabolites in Down syndrome and Alzheimer's disease. Elevated neuroprotective metabolites are found in Down syndrome without cognitive decline. Significant differences in neurotoxic metabolites among study groups were analyzed. There is a potential link between kynurenine pathway dysregulation and cognitive decline. The study provides insights into metabolic changes in aging and neurodegeneration.
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.
HIGHLIGHTS: There are altered kynurenine pathway metabolites in Down syndrome and Alzheimer's disease. Elevated neuroprotective metabolites are found in Down syndrome without cognitive decline. Significant differences in neurotoxic metabolites among study groups were analyzed. There is a potential link between kynurenine pathway dysregulation and cognitive decline. The study provides insights into metabolic changes in aging and neurodegeneration.