Patients with Neurodegenerative Proteinopathies Exhibit Altered Tryptophan Metabolism in the Serum and Cerebrospinal Fluid

0586699 - ÚEB 2025 RIV US eng J - Článek v odborném periodiku
Kaleta, Michal - Hényková, Eva - Menšíková, K. - Friedecký, D. - Kvasnička, A. - Klíčová, K. - Koníčková, D. - Strnad, Miroslav - Kaňovský, P. - Novák, Ondřej
Patients with Neurodegenerative Proteinopathies Exhibit Altered Tryptophan Metabolism in the Serum and Cerebrospinal Fluid.
ACS Chemical Neuroscience. Roč. 15, č. 3 (2024), s. 582-592. ISSN 1948-7193. E-ISSN 1948-7193
Institucionální podpora: RVO:61389030
Klíčová slova: progressive supranuclear palsy * multiple system atrophy * clusterin csf levels * parkinsons-disease * alzheimers-disease * differential-diagnosis * lewy bodies * dementia * biomarkers * substances * Tryptophan metabolic pathway * neurodegenerative disease * Parkinson's disease * Alzheimer's disease * serum * cerebrospinal fluid
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1021/acschemneuro.3c00611

Some pathological conditions affecting the human body can also disrupt metabolic pathways and thus alter the overall metabolic profile. Knowledge of metabolic disturbances in specific diseases could thus enable the differential diagnosis of otherwise similar conditions. This work therefore aimed to comprehensively characterize changes in tryptophan metabolism in selected neurodegenerative diseases. Levels of 18 tryptophan-related neuroactive substances were determined by high throughput and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry in time-linked blood serum and cerebrospinal fluid samples from 100 age-matched participants belonging to five cohorts: healthy volunteers (n = 21) and patients with Lewy body disease (Parkinson's disease and dementia with Lewy bodies, n = 31), four-repeat tauopathy (progressive supranuclear palsy and corticobasal syndrome, n = 10), multiple system atrophy (n = 13), and Alzheimer's disease (n = 25). Although these conditions have different pathologies and clinical symptoms, the discovery of new biomarkers is still important. The most statistically significant differences (with p-values of <= 0.05 to <= 0.0001) between the study cohorts were observed for three tryptophan metabolites: l-kynurenine in cerebrospinal fluid and 3-hydroxy-l-kynurenine and 5-hydroxy-l-tryptophan in blood serum. This led to the discovery of distinctive correlation patterns between the profiled cerebrospinal fluid and serum metabolites that could provide a basis for the differential diagnosis of neurodegenerative tauopathies and synucleinopathies. However, further large-scale studies are needed to determine the direct involvement of these metabolites in the studied neuropathologies, their response to medication, and their potential therapeutic relevance.
Trvalý link: https://hdl.handle.net/11104/0354134