Objective: Parkin is known as the causative gene of autosomal recessive familial Parkinson’s disease (parkin-PD). It remains unclear how parkin dysfunction associates with the dopaminergic degeneration. Additionally, it is controversy whether heterozygous parkin mutations are a risk factor for PD. In this study, we aimed to elucidate the metabolic alterations in parkin-PD compared with healthy subjects.

Background: Recently, serum and/or plasma metabolomics are useful for revealing alterations in metabolic pathways that are related to the pathomechanisms of idiopathic PD (iPD). We hypothesized that the serum metabolomics of patients with homozygous or heterozygous parkin mutations might reveal the pathogenic metabolic alterations due to parkin dysfunction.

Methods: We enrolled 18 patients with parkinsonism (51.7 ± 15.7 years) due to homozygous (7 cases), compound heterozygous (8 cases) and heterozygous (3 cases) and 19 healthy age-matched controls (51 ± 11.52 years). We analyzed a total of 830 metabolites from participants’ serums which have already been well established by metabolomics technologies, including ultrahigh performance liquid chromatography-tandem mass spectroscopy.

Results: Hierarchical matrix analyses can divide samples between controls and parkin-PD based on their metabolic profiles. Metabolic profiles of heterozygous parkin-PD showed similar pattern compared with those of homozougous parkin-PD. Parkin-PD profiles had significantly higher levels of fatty acids metabolites and significantly lower levels of caffeine and benzoate-related metabolites.

Conclusions: Metabolomics analysis can reveal the specific metabolic alterations in parkin-PD, compared with control subjects. The alteration of FA metabolites in parkin-PD indicate the relationship between parkin function and lipid metabolism. Decreasing benzoate-related metabolites might be associated with the alteration of gut microbiota consequently caffeine and its metabolite might be decreased in parkin-PD.

References: Hatano T, Saiki S, Okuzumi A, Mohney RP, Hattori N. Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies. J Neurol Neurosurg Psychiatry 2016;87:295-301. Saiki S, Hatano T, Fujimaki M, et al. Decreased long-chain acylcarnitines from insufficient beta-oxidation as potential early diagnostic markers for Parkinson’s disease. Sci Rep 2017;7:7328.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-putative-serum-biomarkers-for-parkin-related-parkinsons-disease-by-metabolome-analysis/