Abstract
Early diagnosis of Parkinson’s disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. A new ultra performance chromatography mass spectrometry (UPLC-MS/MS) method was developed to quantify plasmatic TAs, and the catecholamines and indolamines pertaining to the same biochemical pathways. Three groups of subjects were recruited: 21 de novo, drug untreated, PD patients, 27 in treatment PD patients and 10 healthy subjects as controls. Multivariate and univariate data analyses were applied to reveal metabolic changes among the groups in attempt to discover new putative markers for early PD detection and disease progression. Different circulating levels of tyrosine (p = 0.002), tyramine (p < 0.001), synephrine (p = 0.015), norepinephrine (p = 0.012), metanephrine (p = 0.001), β-phenylethylamine (p = 0.001) and serotonin (p = 0.006) were found among the three groups. While tyramine behaves as a putative biomarker for early-stage PD (AUC = 0.90) tyramine, norepinephrine, and tyrosine appear to act as biomarkers of disease progression (AUC > 0.75). The findings of this pilot cross-sectional study suggest that biochemical anomalies of the aminergic and indolic neurotransmitters occur in PD patients. Compounds within the TAs family may constitute putative markers for early stage detection and progression of PD.
Highlights
Diagnosis of Parkinson’s disease (PD) remains a challenge to date
TYRA, NE, and TYRO showed power greater than 0.80, raising the possibility that these compounds behave as promising markers for the progression of the disease. This pilot cross-sectional study was designed to assess whether anomalies in the metabolism of trace amines and related organic compounds characterize different stages of PD and, as such, potentially constitute markers for early diagnosis and disease progression
By employing a new UPLC-mass spectrometry (MS)/MS metabolomics method, we provide evidence that metabolic profiles resulting from the hydroxylation and decarboxylation of PHE, TYRO, and TRP are largely perturbed in PD patients
Summary
Diagnosis of Parkinson’s disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. While tyramine behaves as a putative biomarker for early-stage PD (AUC = 0.90) tyramine, norepinephrine, and tyrosine appear to act as biomarkers of disease progression (AUC > 0.75). The findings of this pilot cross-sectional study suggest that biochemical anomalies of the aminergic and indolic neurotransmitters occur in PD patients. In recent years significant research resources have been devoted to the search of clinical or neuroimaging biomarkers in PD, as well as possible other newer markers in biological samples[5] Among the latter, metabolomic profiling has been employed as a tool to identify PD progression biomarkers, to discover novel biomarkers and to predict the development of PD6. TAs are considered as full agonists of TAAR113 and may play a role in the modulation of the central circuits controlling the dopaminergic system
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