Amino Acid Levels as Potential Biomarkers of Multiple Sclerosis in Elderly Patients: Preliminary Report
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Aging in multiple sclerosis is associated with both disease- and age-dependent neurodegeneration. Serum metabolomic profiling of amino acids seems to be a promising method for searching for biomarkers of neurodegenerative disorders. The aim of this study was to determine the profile of nonessential amino acids in the serum of elderly patients with secondary progressive multiple sclerosis (SPMS). Methods We used high-performance liquid chromatography to evaluate the serum concentrations of nonessential amino acids in subjects aged >65 years: six patients with SPMS and 20 control subjects (CS). Results The serine and alanine levels were significantly higher in SPMS patients than in CS, whereas the concentrations of aspartic acid, arginine, and cysteine were significantly lower in SPMS patients. These observations indicate that amino acids may be involved in SPMS neurodegeneration mechanisms. There were no significant differences in the serum concentrations of the other four amino acids investigated (glutamic acid, glycine, proline, and tyrosine) between patients with SPMS and CS. Conclusions The preliminary results obtained in the study suggest that the metabolism of some amino acids is altered in patient with SPMS. We also conclude that amino acid profiling might be helpful in searching for putative biomarkers of central nervous system diseases. However, considering the multifactorial, heterogeneous, and complex nature of SPMS, further validation research involving larger study samples is required before applying these biomarkers in diagnostic practice.
Abstract
Background and Purpose Aging in multiple sclerosis is associated with both disease- and age-dependent neurodegeneration. Serum metabolomic profiling of amino acids seems to be a promising method for searching for biomarkers of neurodegenerative disorders. The aim of this study was to determine the profile of nonessential amino acids in the serum of elderly patients with secondary progressive multiple sclerosis (SPMS). Methods We used high-performance liquid chromatography to evaluate the serum concentrations of nonessential amino acids in subjects aged >65 years: six patients with SPMS and 20 control subjects (CS). Results The serine and alanine levels were significantly higher in SPMS patients than in CS, whereas the concentrations of aspartic acid, arginine, and cysteine were significantly lower in SPMS patients. These observations indicate that amino acids may be involved in SPMS neurodegeneration mechanisms. There were no significant differences in the serum concentrations of the other four amino acids investigated (glutamic acid, glycine, proline, and tyrosine) between patients with SPMS and CS. Conclusions The preliminary results obtained in the study suggest that the metabolism of some amino acids is altered in patient with SPMS. We also conclude that amino acid profiling might be helpful in searching for putative biomarkers of central nervous system diseases. However, considering the multifactorial, heterogeneous, and complex nature of SPMS, further validation research involving larger study samples is required before applying these biomarkers in diagnostic practice.
참고문헌 (28)
- Confavreux C, "Natural history of multiple sclerosis : a unifying concept", Brain, 129(Pt 3), pp.606~616 (2006)
- Lublin FD, "Defining the clinical course of multiple sclerosis : results of an international survey. National Multiple Sclerosis Society(USA)Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis", Neurology, 46, pp.907~911 (1996)
- Montalban X, "ECTRIMS", EAN guideline on the pharmacological treatment of people with multiple sclerosis, 2018, pp.25, 215~237
- Cottrell DA, "The natural history of multiple sclerosis : a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis", Brain, 122(Pt 4), pp.625~639 (1999)
- Miller DH, "Primary-progressive multiple sclerosis", Lancet Neurol, 6, pp.903~912 (2007)
- Tremlett H, "Primary and secondary progressive MS have a similar age at onset of progression-NO", Mult Scler, 23, pp.640~642 (2017)
- Lorscheider J, "Defining secondary progressive multiple sclerosis", Brain, 139(Pt 9), pp.2395~2405 (2016)
- Rzepiński Ł, "Early clinical features, time to secondary progression, and disability milestones in polish multiple sclerosis patients", Medicina(Kaunas), 55, pp.232~ (2019)
- Katz Sand I, "Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis", Mult Scler, 20, pp.1654~1657 (2014)
- Dumitrescu L, "Siponimod for the treatment of secondary progressive multiple sclerosis", Expert Opin Pharmacother, 20, pp.143~150 (2019)
- Socha E, "Amino acid profiling as a method of discovering biomarkers for diagnosis of neurodegenerative diseases", Amino Acids, 51, pp.367~371 (2019)
- Adachi Y, "Plasma amino acid profile in severely frail elderly patients in Japan", Int J Gerontol, 12, pp.290~293 (2018)
- Corso G, "Serum amino acid profiles in normal subjects and in patients with or at risk of Alzheimer dementia", Dement Geriatr Cogn Dis Extra, 7, pp.143~159 (2017)
- Figura M, "Serum amino acid profile in patients with Parkinson’s disease", PLoS One, 13, pp.e0191670~ (2018)
- Herman S, "Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis", Theranostics, 8, pp.4477~4490 (2018)
- Polman CH, "Diagnostic criteria for multiple sclerosis : 2010 revisions to the McDonald criteria", Ann Neurol, 69, pp.292~302 (2011)
- Kurtzke JF, "Rating neurologic impairment in multiple sclerosis : an expanded disability status scale(EDSS)", Neurology, 33, pp.1444~1452 (1983)
- Bermel RA, "Unravelling neurodegeneration in multiple sclerosis", Lancet Neurol, 16, pp.764~766 (2017)
- Poser CM, "Amino acid residues of serum and CSF protein in multiple sclerosis", Trans Am Neurol Assoc, 99, pp.235~237 (1974)
- Kasakin MF, "Changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls", Mult Scler Int, 2020, pp.9010937~ (2020)
- Sarchielli P, "Excitatory amino acids and multiple sclerosis : evidence from cerebrospinal fluid", Arch Neurol, 60, pp.1082~1088 (2003)
- Al Gawwam G, "Serum glutamate is a predictor for the diagnosis of multiple sclerosis", ScientificWorldJournal, 2017, pp.9320802~ (2017)
- Haghikia A, "Serum and cerebrospinal fluid concentrations of homoarginine, arginine, asymmetric and symmetric dimethylarginine, nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica", Amino Acids, 47, pp.1837~1845 (2015)
- Virarkar M, "L-arginine and nitric oxide in CNS function and neurodegenerative diseases", Crit Rev Food Sci Nutr, 53, pp.1157~1167 (2013)
- Rejdak K, "CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis", Neurology, 63, pp.1439~1445 (2004)
- Porter L, "Metabolomic biomarkers of multiple sclerosis : a systematic review", Front Mol Biosci, 7, pp.574133~ (2020)
- Poddighe S, "Metabolomic analysis identifies altered metabolic pathways in multiple sclerosis", Int J Biochem Cell Biol, 93, pp.148~155 (2017)
- Reinke SN, "Metabolomic profiling in multiple sclerosis : insights into biomarkers and pathogenesis", Mult Scler, 20, pp.1396~1400 (2014)
