Anna Picca1, Riccardo Calvani1, Giovanni Landi2, Federico Marini3, Alessandra Biancolillo4, Jacopo Gervasoni1, Silvia Persichilli1, Aniello Primiano2, Andrea Urbani1, Maurizio Bossola5, Anna Rita Bentivoglio6, Matteo Cesari7, Francesco Landi1, Roberto Bernabei8, Emanuele Marzetti9, Maria Rita Lo Monaco2. 1. Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, Rome, Italy; Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy. 2. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy. 3. Department of Chemistry, Sapienza Università di Roma, Rome, Italy. 4. Department of Chemistry, Sapienza Università di Roma, Rome, Italy; Department of Physical and Chemical Sciences, University of L'Aquila, Italy. 5. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Institute of Clinical Surgery, Rome, Italy. 6. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Institute of Neurology, Rome, Italy. 7. Department of Clinical Sciences and Community Health, Università di Milano, Milan, Italy; Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, Rome, Italy; Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy. Electronic address: roberto.bernabei@unicatt.it. 9. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy. Electronic address: emanuele.marzetti@policlinicogemelli.it.
Abstract
BACKGROUND AND AIM: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. PARTICIPANTS AND METHODS: Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares - discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. RESULTS: The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. CONCLUSION: Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.
BACKGROUND AND AIM: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. PARTICIPANTS AND METHODS: Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares - discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. RESULTS: The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. CONCLUSION: Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.
Authors: Federica Murgia; Luigi Atzori; Ezio Carboni; Maria Laura Santoru; Aran Hendren; Augusta Pisanu; Pierluigi Caboni; Laura Boi; Giuliana Fusco; Anna R Carta Journal: Int J Mol Sci Date: 2020-09-14 Impact factor: 5.923