Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson’s disease: review and meta‐analysis

Abstract

Background and purpose: The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of Parkinson's disease (PD). Methods: This is a review of four databases (PubMed, Embase, MED-LINE and Web of Science-Core Collection) from 1966 to 14 March 2020, with identification of references of interest for the topic. The metaanalysis of eligible studies was done using R software package meta, following the PRISMA and MOOSE guidelines. Results: Compared with age-and sex-matched controls, PD patients showed decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan and lysine, and increased serum/plasma proline and homocysteine levels. Conclusion: Despite the 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 patients from healthy subjects, related to the levels of some amino acids. Methods Search strategy A complete literature search was undertaken, without language restrictions, using four databases (PubMed,

The Metabolomic Approach Reveals the Alteration in Human Serum and Cerebrospinal Fluid Composition in Parkinson’s Disease Patients

“…Analyzing the CSF and the serum of PD and APDs patients, we found increased levels of trans-4-hydroxyproline compared to controls, but not between the PD and APDs groups. Jimenez et al summed up the studies presenting blood amino acids evaluations, including some studies showing elevated levels of 4-hydroxyproline in PD patients [ 38 ]. Our results, indicating an increased level of hydroxyproline, are in line with these observations.…”

“…It is the precursor of L-dopa, which is converted into the neurotransmitter dopamine, which is, in turn, a precursor of noradrenaline and adrenaline. Increased tyrosine concentrations in the CSF of PD patients could hypothetically be related to an attempt by dopaminergic cells of the brain to increase the synthesis of dopamine in a situation of dopaminergic neuron depletion [ 38 ]. This statement is in line with our research on targeted metabolomics, where the levels of tyrosine in both of the studied matrices (CSF and serum) were elevated in PD patients compared to the control group.…”

ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype

“…We further demonstrate an accumulation of tyrosine in CSF of patients with ASLD even after liver transplantation. Interestingly, patients with PD have also been shown to have high levels of tyrosine in their CSF (56,57), and nitrotyrosine immunoreactivity has been found in the core of Lewy bodies within degenerating neurons in brains from individuals with PD (50), supporting the relevance of tyrosine accumulation in this disorder. Collectively, our data may suggest that neurons of the SNc depend on TH for dopamine synthesis and are hence particularly sensitive to tyrosine accumulation.…”

Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

“…Additionally, ornithine accumulation leads to higher proline levels, which could induce collagen biosynthesis, leading to a shift in the immune system towards a program of wound healing [ 303 ]. Increased levels of trans-4-hydroxyproline were found in the CSF and sera of patients with PD—possibly partially caused by the intensified degradation of collagen [ 302 , 304 ].…”