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Research paper
Identification of novel biomarkers for Parkinson's disease by metabolomic technologies
  1. Taku Hatano1,
  2. Shinji Saiki1,
  3. Ayami Okuzumi1,
  4. Robert P Mohney2,
  5. Nobutaka Hattori1,3
  1. 1Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
  2. 2Metabolon Inc., Durham, North Carolina, USA
  3. 3Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan
  1. Correspondence to Dr Nobutaka Hattori, Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; nhattori{at}juntendo.ac.jp

Abstract

Objective The pathogenesis of Parkinson's disease (PD) involves complex interactions between environmental and genetic factors. Metabolomics can shed light on alterations in metabolic pathways in many diseases, including neurodegenerative diseases. In the present study, we attempted to elucidate the candidate metabolic pathway(s) associated with PD.

Methods Serum samples were collected from 35 individuals with idiopathic PD without dementia and 15 healthy age-matched control participants without PD. This analysis used a combination of three independent platforms: ultrahigh-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) optimised for basic species, UPLC/MS/MS optimised for acidic species and gas chromatography/MS (GC/MS).

Results The metabolomic profiles of PD were clearly different from normal controls. PD profiles had significantly lower levels of tryptophan, caffeine and its metabolites, bilirubin and ergothioneine, and significantly higher levels of levodopa metabolites and biliverdin than those of normal controls. Alterations in the bilirubin/biliverdin ratio and ergothioneine can indicate oxidative stress intensity and may suggest elevated oxidative stress and/or insufficient ability for scavenging free radicals, which could contribute to PD pathogenesis. Decreased serum tryptophan level is associated with psychiatric problems in PD. A decrease in serum caffeine levels is consistent with an inverse association of caffeine consumption with development of PD based on past epidemiological studies.

Conclusions Metabolomic analysis detected biomarkers associated with PD pathogenesis and disease progression. Since critical metabolic biomarkers need to be identified in PD, future studies should include assay validation and replication in independent cohorts.

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