Trace amines, the product of the metabolism of specific amino acids, could indicate changes that occur early during Parkinson’s disease and may serve as early-stage and disease progression biomarkers, a study suggests.
The study, “Different Circulating Trace Amine Profiles in De Novo and Treated Parkinson’s Disease Patients,” was published in Scientific Reports.
Parkinson’s disease is caused by the loss of dopaminergic neurons — those that produce dopamine — and is mostly recognized by motor symptoms that appear during the middle and later stages of the disease.
Although Parkinson’s actually begins years before the appearance of the first motor manifestations, diagnosing the disease in its early stages is a challenge, mainly because there are no reliable biomarkers.
Previous studies have suggested that disturbances in the metabolism of amino acids — the building blocks of proteins — fatty acids, and in the function of mitochondria (which provide energy to cells) occur during the early stages of Parkinson’s.
Therefore, the levels of trace amines — a group of different molecules that originate during the metabolism of specific amino acids — could indicate different stages of Parkinson’s progression, and could be used as potential biomarkers.
However, trace amines are present in very low concentrations both in the central nervous system and in the blood, which makes it difficult to accurately measure and compare their levels.
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Researchers have now used a new method — called ultra performance chromatography-mass spectrometry (UPLC-MS/MS) — that allows them to quantify even very low amounts of a specific molecule with high sensitivity and evaluate the differences in trace amine levels caused as a consequence of Parkinson’s progression.
They recruited three patient groups: 21 patients (mean age, 64 years) who had been diagnosed for less than two years and had not received any Parkinson’s-related medication; 27 patients (mean age, 69 years) who had been diagnosed for less than five years and were receiving treatment; 10 healthy individuals (mean age, 61 years) who served as controls.
The researchers found that each group had a specific trace amine profile. For example, the healthy group had lower levels of tyramine and higher levels of beta-phenylethylamine, the non-treated group had higher levels of tryptamine and low levels of tryptophan, and the treated group had overall lower levels of trace amines.
They then compared the profile of the healthy participants to that of non-treated patients to identify possible markers of early-stage Parkinson’s and found that tyramine was the best candidate.
They also compared the profile of treated and non-treated groups to identify possible biomarkers of disease progression and found that a combination of tyramine, norepinephrine, and tyrosine showed satisfactory results.
The changes in trace amines indicate that specific metabolic pathways are altered during the early stages of Parkinson’s and that these metabolic changes continue as the disease progresses.
“Regardless of the metabolic pathways involved, our results show, to our knowledge for the first time, that circulating levels of [trace amines] may constitute disease-related metabolic biomarkers in [Parkinson’s disease],” the researchers wrote.
A limitation of the study is that the patients with middle to late stage Parkinson’s were taking medication during the study, and therefore it was not possible to distinguish which changes were caused by disease progression and which could have been influenced as a result of treatment.
“[Trace amine] when assessed in the circulation, have the potential to provide for disease biomarkers, either alone or in combination with other markers. Also, should these changes mirror ongoing changes in the hypothalamus and other dopaminergic centers within the [central nervous system], it is possible that pharmacological agents modulating [trace amine] receptors may represent new avenues in the prevention and/or treatment of [Parkinson’s disease],” the researchers concluded.