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

Abstract

Parkinson’s disease (PD) is a major public health problem. Since currently there are no reliable diagnostic tools to reveal the early steps of PD, new methods should be developed, including those searching the variations in human metabolome. Alterations in human metabolites could help to establish an earlier and more accurate diagnosis. The presented research shows a targeted metabolomics study of both of the serum and CSF from PD patients, atypical parkinsonian disorders (APDs) patients, and the control. The use of the LC-MS/MS system enabled to quantitate 144 analytes in the serum and 51 in the CSF. This information about the concentration enabled for selection of the metabolites useful for differentiation between the studied group of patients, which should be further evaluated as candidates for markers of screening and differential diagnosis of PD and APDs. Among them, the four compounds observed to be altered in both the serum and CSF seem to be the most important: tyrosine, putrescine, trans-4-hydroxyproline, and total dimethylarginine. Furthermore, we indicated the metabolic pathways potentially related to neurodegeneration processes. Our studies present evidence that the proline metabolism might be related to neurodegeneration processes underlying PD and APDs. Further studies on the proposed metabolites and founded metabolic pathways may significantly contribute to understanding the molecular background of PD and improving the diagnostics and treatment in the future.

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

“…Proline is involved in aging and neurodegeneration [ 300 , 301 ]. In this regard, a recent study found high concentration levels of ornithine—the precursor of proline—in the sera of patients with PD [ 302 ], confirming results obtained by Çelik et al [ 303 ]. Ornithine accumulation is associated with hyperosmolarity in different regions of the brain via urea cycle flux [ 303 ].…”

“…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 ].…”

Update on CSF Biomarkers in Parkinson’s Disease

“…Metabolomics has attracted attention in recent years, revealing multiple novel metabolic pathways linked to the pathogenesis of PD. Several studies demonstrated altered metabolic profiles in PD, PD subgroups, APS and other neurological conditions [ 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. By utilizing machine learning algorithms, 14 CSF metabolites were identified that enabled distinguishing early PD from controls with high accuracy [ 104 ].…”

“…Moreover, a link between altered metabolic profiles and the tricarboxylic acid cycle has been observed, which are implicated in mitochondrial dysfunction and increased oxidative stress [ 106 ]. By using liquid chromatography–tandem mass spectrometry, a recently published study detected increased CSF levels of intermediates of the proline metabolic pathway in PD and APS subjects that could discriminate them from controls but not among parkinsonian syndromes [ 97 ].…”

Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy

“…Besides these, many altered metabolites in the CSF of patients with PD compared with controls have been reported. The levels of trans-4-hydroxyproline [62], α-N-phenylacetyl-L-glutamine [63], (+)-gammahydroxy-L-homoarginine [63], p-cresol sulfate [64], decanoic acid [64], 10-hydroxydecanoic acid [64], dihomo-γ-linolenic acid [64], and diacylglycerol [65] have been shown to be increased, while those of betaine [63], dimethylglycine [63], α-aminobutyric acid [66], ornithine [66], lysine [66], and histidine [66] have been shown to be decreased.…”