The review, “Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson’s Disease: review and meta‐analysis,” was published in the European Journal of Neurology.
A definitive diagnosis of idiopathic Parkinson’s — when the disease has no known cause — can only be made after death, upon the examination of patients’ brain tissue samples post-mortem. Thus, doctors must focus largely on clinical criteria that identify Parkinson’s typical symptoms in diagnosing people with the disease.
This has encouraged researchers to look for possible biomarkers that could be used in addition to clinical examination to distinguish patients with Parkinson’s from those with other parkinsonian syndromes and healthy individuals.
To date, studies exploring the value of several amino acids found in the blood and cerebrospinal fluid (CSF) — the liquid that surrounds the brain and spinal cord — as biomarkers of Parkinson’s have been inconclusive.
According to the researchers, this “may be related with several factors such as sample size, differences in the handling and storage of samples or in the study methodologies, … and differences in anti-parkinsonian therapies.”
This review and meta-analysis aimed to determine if the levels of certain amino acids circulating in the blood and CSF could be valuable biomarkers of Parkinson’s.
Using four online databases — PubMed, EMBASE, MedLine, and Web of Science — to search the literature, the researchers identified a total of 1,927 studies published between 1966 and 2020 that focused on assessing the possible value of amino acids as biomarkers of Parkinson’s.
After removing duplicates and excluding studies that lacked a proper control group or had other flaws in methodology, the team selected 32 to review.
A pooled analysis of 19 studies comparing the levels of 32 amino acids found in the CSF of those with and without Parkinson’s showed that people with the disease tended to have lower levels of glutamate — an important transmitter for normal brain function — and higher levels of threonine and tyrosine compared with controls. Threonine is an immunostimulant that promotes the growth of the thymus gland, while tyrosine is a precursor for neurotransmitters, including dopamine, that are an important part of the body’s sympathetic nervous system.
The investigators then did a similar analysis using only studies in which patients had been matched to healthy individuals of the same sex and approximately the same age. The findings showed that those with Parkinson’s had lower levels of glutamate and taurine — which has many diverse biological functions, including serving as a neurotransmitter in the brain — and higher levels of tyrosine in their CSF compared with controls.
Next, studies that compared amino acid levels in the blood were evaluated. The researchers did a pooled analysis of the 18 studies comparing the levels of 36 amino acids found in the blood of Parkinson’s patients and matched healthy people (controls). These results showed that individuals with the disease tended to have lower levels of aspartate, serine, tryptophan, and lysine compared with the healthy controls. The Parkinson’s patients also had higher levels of proline and homocysteine compared with the controls. These amino acids, like all building blocks of proteins and peptides, become essential under certain conditions.
“Despite limitations of this study due to the important variability of results between different series, our findings suggest the value of CSF or serum/plasma levels of several amino acids in the discrimination of PD [Parkinson’s disease] patients from healthy subjects,” the researchers wrote.
The investigators noted that future studies attempting to establish amino acids as biomarkers of Parkinson’s should follow a large number of patients and matched controls over a long period of time. Such studies also need to ensure that the collection and handling of CSF and blood samples are performed regularly using the same conditions.
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