Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease

Abstract

ObjectiveTo investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography–mass spectrometry.MethodsLevels 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.ResultsSerum 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.ConclusionAbsolute 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 evidenceThis study provides Class III evidence that decreased serum levels of caffeine and its metabolites identify patients with PD.

A metabolic profile of polyamines in parkinson disease: A promising biomarker

“…16,[36][37][38] DiAcSpd levels clearly correlated with both H&Y and UPDRS-III under age-or medication-normalized conditions, and significantly correlated with FA (an index of white matter integrity alterations), in diffuse white matter, similar to our previous report. Notably, even using a multivariate model, DiAcSpd remained significantly correlated with disease severity.…”

“…However, surrogate biomarkers reflecting age-related pathogeneses have not been established. 16,[36][37][38] DiAcSpd levels clearly correlated with both H&Y and UPDRS-III under age-or medication-normalized conditions, and significantly correlated with FA (an index of white matter integrity alterations), in diffuse white matter, similar to our previous report. 34,39 Likewise, higher diagnostic power of DiAcSpd levels was confirmed.…”

Metabolomics‐based identification of metabolic alterations in PARK2

“…Therefore, Berg et al., suggested that decreasing caffeine consumption was one of the risks of prodromal iPD . Furthermore, we revealed that serum levels of caffeine and its metabolites are significantly decreased in iPD, despite no difference in caffeine consumption between patients and controls . Interestingly, similar to iPD, our results here also indicate decreased serum levels of caffeine and its metabolites in PARK2.…”

“…Screening was also performed for polymorphisms of cytochrome P450 family 1, subfamily A (CYP1A) and cytochrome P450 famil y 2, s ubfamily E member 1 (CYP2E1) , which are involved in metabolism of xenobiotics including caffeine and its metabolites. The genetic analysis methods have been previously described . Data were collected between March 2014 and April 2016.…”

Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

“…Although patients with atypical parkinsonism were also taking antiparkinsonian drugs, including levodopa, dopamine agonists, and MAOB inhibitors, the %HNA of these patients was similar to healthy subjects. Additionally, in recent reports, a metabolomics analysis in iPD revealed that antiparkinsonian drugs are less effective on their metabolites; therefore, we consider that antiparkinsonian drugs had little influence on the results. Fourth, a longitudinal study should be conducted to establish a direct association between hyperoxidative albuminemia and disease progression.…”