Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease
Fujimaki M, Saiki S, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N
Neurology · 69 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Case-control study (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Japan Society for the Promotion of Science
- Authors
- At least one author declares a financial tie to industry
- Grants
- Japan Society for the Promotion of Science (15KK0354); Japan Society for the Promotion of Science (18K07829); Japan Society for the Promotion of Science (16K09675); Japan Society for the Promotion of Science (17K07797); Japan Society for the Promotion of Science (15H04843); Japan Society for the Promotion of Science (16K09676); Japan Society for the Promotion of Science (16K01834)
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-01-04 · Neurology · vol. 90 · issue 5 · pp. e404–e411
- Publisher
- Lippincott Williams & Wilkins
- Cited
- 103 citations · more than 98% of similar papers · 8.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 40 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Coffee research and impacts · Parkinson's Disease Mechanisms and Treatments · Adenosine and Purinergic Signaling
- Keywords
- Caffeine, Metabolite, CYP1A2, Paraxanthine, Adenosine receptor, Biomarker, Parkinson's disease, Internal medicine, Area under the curve, Chemistry, Metabolomics, Pharmacology, Endocrinology, Medicine, Receptor, Cytochrome P450, Metabolism, Biochemistry, Disease, Chromatography
- MeSH
- humans, parkinson disease, 3-iodobenzylguanidine, caffeine, cytochrome p-450 cyp1a2, cytochrome p-450 cyp2e1, chromatography, liquid, severity of illness index, case-control studies, retrospective studies, mutation, aged, middle aged, female, male, mass spectrometry, myocardial perfusion imaging, biomarkers
17 authors
- Motoki Fujimaki
- Shinji Saiki
- Yuanzhe Li
- Naoko Kaga
- Hikari Taka
- Taku Hatano
Abstract
Objective
To investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography-mass spectrometry.
Methods
Levels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age-matched healthy controls were examined by liquid chromatography-mass spectrometry. Mutations in caffeine-associated genes were screened by direct sequencing.
Results
Serum levels of caffeine and 9 of its downstream metabolites were significantly decreased even in patients with early PD, unrelated to total caffeine intake or disease severity. No significant genetic variations in CYP1A2 or CYP2E1, encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine in humans, were detected compared with controls. Likewise, caffeine concentrations in patients with PD with motor complications were significantly decreased compared with those without motor complications. No associations between disease severity and single nucleotide variants of the ADORA2A gene encoding adenosine 2A receptor were detected, implying a dissociation of receptor sensitivity changes and phenotype. The profile of serum caffeine and metabolite levels was identified as a potential diagnostic biomarker by receiver operating characteristic curve analysis.
Conclusion
Absolute lower levels of caffeine and caffeine metabolite profiles are promising diagnostic biomarkers for early PD. This is consistent with the neuroprotective effect of caffeine previously revealed by epidemiologic and experimental studies.
Classification of evidence
This study provides Class III evidence that decreased serum levels of caffeine and its metabolites identify patients with PD.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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