Abstract
Differentiating between Parkinson’s disease (PD) and the atypical Parkinsonian disorders of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) is difficult clinically due to overlapping symptomatology, especially at early disease stages. Consequently, there is a need to identify metabolic markers for these diseases and to develop them into viable biomarkers. In the present investigation, solution nuclear magnetic resonance and mass spectrometry metabolomics were used to quantitatively characterize the plasma metabolomes (a total of 167 metabolites) of a cohort of 94 individuals comprising 34 PD, 12 MSA, and 17 PSP patients, as well as 31 control subjects. The distinct and statistically significant differences observed in the metabolite concentrations of the different disease and control groups enabled the identification of potential plasma metabolite markers of each disorder and enabled the differentiation between the disorders. These group-specific differences further implicate disturbances in specific metabolic pathways. The two metabolites, formic acid and succinate, were altered similarly in all three disease groups when compared to the control group, where a reduced level of formic acid suggested an effect on pyruvate metabolism, methane metabolism, and/or the kynurenine pathway, and an increased succinate level suggested an effect on the citric acid cycle and mitochondrial dysfunction.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and intraneuronal α-synuclein-rich protein aggregates (Lewy bodies and Lewy neurites) [1,2]
Nuclear magnetic resonance (NMR)-Based Analysis The recorded 1H-NMR spectra of the 94 filtered plasma samples were analyzed in the Chenomx software, and a total of 49 metabolites were identified, and of these 34 were quantified in all samples
A previous study using plasma did not observe any changes in arginine concentration [21], and a study in serum found a reduced concentration [29]; the use of different methods, liquid chromatography compared to NMR spectroscopy, may contribute to the observed discrepancies
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and intraneuronal α-synuclein-rich protein aggregates (Lewy bodies and Lewy neurites) [1,2]. Diagnosis of PD is based on the presence of bradykinesia and at least one other symptom of resting tremor, rigidity, and postural instability [3]. Additional motor and non-motor symptoms are frequently observed [2]. MSA is similar to PD an α-synucleinopathy, but with deposits primarily in the glial cell population, whereas PSP instead is a tauopathy displaying neurofibrillary tangles of the tau protein. Both MSA and PSP are further divided into subgroups where those with a Parkinsonian symptomatology are denoted MSA-P and PSP-P, respectively
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