Sadhana Kumari1, S Senthil Kumaran2, Vinay Goyal3, Raj Kumar Sharma4, Neeraj Sinha4, S N Dwivedi5, Achal Kumar Srivastava6, N R Jagannathan7. 1. NMR and MRI Facility, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. 2. NMR and MRI Facility, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. Electronic address: senthil@aiims.edu. 3. Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India; Director Neurology, Medanta, The Medicity, Gurgaon, India. 4. Centre of Biomedical Research, SGPGI Campus, Lucknow, India. 5. Department of Biostatistics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. 6. Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. 7. NMR and MRI Facility, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India; Professor of Eminence of Radiology, Chettinad Academy of Research & Education, Kelambakkam, TN 603103, India.
Abstract
INTRODUCTION: Parkinson's disease (PD) is the most common neurodegenerative disease caused by the loss of dopamine chemicals resulting in urinary incontinence, gastrointestinal dysfunction, gait impairment and mitochondrial dysfunction. Study investigated urinary metabolic profiles of patients with idiopathic PD as compared to healthy controls (HC) to identify the potential biomarkers. METHODS: Urine samples were collected from 100 PD subjects and 50 HC using standard protocol. Metabolomic analyses were performed using high resolution nuclear magnetic resonance (NMR) spectroscopy. The integral values of 17 significant metabolites were estimated and concentration values were calculated, which were subjected to univariate and multivariate statistical analysis. RESULTS: We found significantly increased levels of ornithine, phenylalanine, isoleucine, β-hydroxybutyrate, tyrosine and succinate in the urine of patients with PD in comparison with HC. These metabolites exhibited area under the curve greater than 0.60 on ROC curve analysis. We also observed a significant association between succinate concentration and UPDRS motor scores of PD. DISCUSSION: Metabolic pathway alterations were observed in aromatic amino acid metabolism, ketone bodies synthesis, branched chain amino acid metabolism and ornithine metabolism. Comprehensive metabolomic profiling revealed variations in urinary signatures associated with severity of idiopathic PD. This profiling relies on non-invasive sampling and is complementary to existing clinical modalities.
INTRODUCTION:Parkinson's disease (PD) is the most common neurodegenerative disease caused by the loss of dopamine chemicals resulting in urinary incontinence, gastrointestinal dysfunction, gait impairment and mitochondrial dysfunction. Study investigated urinary metabolic profiles of patients with idiopathic PD as compared to healthy controls (HC) to identify the potential biomarkers. METHODS: Urine samples were collected from 100 PD subjects and 50 HC using standard protocol. Metabolomic analyses were performed using high resolution nuclear magnetic resonance (NMR) spectroscopy. The integral values of 17 significant metabolites were estimated and concentration values were calculated, which were subjected to univariate and multivariate statistical analysis. RESULTS: We found significantly increased levels of ornithine, phenylalanine, isoleucine, β-hydroxybutyrate, tyrosine and succinate in the urine of patients with PD in comparison with HC. These metabolites exhibited area under the curve greater than 0.60 on ROC curve analysis. We also observed a significant association between succinate concentration and UPDRS motor scores of PD. DISCUSSION: Metabolic pathway alterations were observed in aromatic amino acid metabolism, ketone bodies synthesis, branched chain amino acid metabolism and ornithine metabolism. Comprehensive metabolomic profiling revealed variations in urinary signatures associated with severity of idiopathic PD. This profiling relies on non-invasive sampling and is complementary to existing clinical modalities.
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Authors: Nathan Hwangbo; Xinyu Zhang; Daniel Raftery; Haiwei Gu; Shu-Ching Hu; Thomas J Montine; Joseph F Quinn; Kathryn A Chung; Amie L Hiller; Dongfang Wang; Qiang Fei; Lisa Bettcher; Cyrus P Zabetian; Elaine R Peskind; Ge Li; Daniel E L Promislow; Marie Y Davis; Alexander Franks Journal: Metabolites Date: 2022-03-22