Metabolomic biomarkers as strong correlates of Parkinson disease progression

LeWitt, Peter A.; Li, Jia; Lü, Mei; Guo, Lining; Auinger, Peggy

doi:10.1212/wnl.0000000000003663

Cited by 122 publications

(96 citation statements)

References 35 publications

(46 reference statements)

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“…Among our studies, the CSF compounds corresponding to the diagnosis of PD were not the same biochemicals that were found to correlate with the progression of PD . The latter set of compounds also differed from the metabolomic profile in postmortem CSF specimens discovered to distinguish PD from controls …”

contrasting

confidence: 51%

“…Trezzi and colleagues linked their biochemical findings to a plausible explanation for PD pathogenesis implicating oxidative stress. Whereas the search for biomarkers may be rewarded with insights into the disease process (such as involvement of the kynurenine pathway), it also might be a scientific conceit that the altered concentrations of compounds should necessarily point to the mechanisms of neurodegeneration. It seems possible that even the most robust biomarkers chosen by metabolomics might actually be no more than epiphenomena of the disease process.…”

mentioning

confidence: 99%

“…3 The latter set of compounds also differed from the metabolomic profile in postmortem CSF specimens discovered to distinguish PD from controls. 4 Why should there be such diverse results among seasoned researchers utilizing large groups of specimen, standardized collection methods, sophisticated assay techniques, and established biostatistical tools? The answer may be the challenge inherent in studying CSF as the source of biomarkers.…”

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confidence: 99%

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Comment on ‘Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease’ by Hiller et al

LeWitt

2018

Movement Disorders

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confidence: 51%

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confidence: 99%

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confidence: 99%

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Comment on ‘Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease’ by Hiller et al

LeWitt

2018

Movement Disorders

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“…Recently, we and other groups revealed that serum and/or plasma metabolomics are useful for identifying alterations in metabolic pathways associated with the pathological condition of iPD . In iPD, pathological alterations in the peripheral nervous system, such as peripheral vagus nerve degeneration with α‐synuclein deposition, are observed from an early stage.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics‐based identification of metabolic alterations in PARK2

Okuzumi

Hatano

Ueno

et al. 2019

Ann Clin Transl Neurol

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Objective Parkin is the causative gene for autosomal recessive familial Parkinson's disease (PD), although it remains unclear how parkin dysfunction is involved with the general condition. Recently, serum and/or plasma metabolomics revealed alterations in metabolic pathways that might reflect pathomechanisms of idiopathic PD (iPD). Thus, we hypothesized that serum metabolomics of patients with homozygous or compound heterozygous parkin mutations (namely, PARK2) might reflect metabolic alterations due to parkin dysfunction. Methods We enrolled 15 PARK2 patients (52 ± 17.6 years) confirmed with homozygous (seven cases) and compound heterozygous (eight cases) parkin mutations, along with 19 healthy age‐matched controls (51 ± 11.5 years). We analyzed 830 metabolites from participants’ serum using well‐established metabolomics technologies, including ultra‐high performance liquid chromatography/tandem mass spectroscopy. Results Based on metabolic profiles, hierarchical matrix analysis can divide samples between control and PARK2 subjects. Profiles from PARK2 patients showed significantly higher levels of fatty acid (FA) metabolites and oxidized lipids, and significantly lower levels of antioxidant, caffeine, and benzoate‐related metabolites. Interpretation Metabolomics can identify specific metabolic alterations in PARK2 patients compared with controls. Alterations in FA metabolites suggest a relationship between parkin function and lipid metabolism. The elevation of oxidized lipids in combination with decreasing antioxidants may reflect general hyperoxidative stress. Decreasing benzoate‐related metabolites might be due to the alteration in gut microbiota. Consequently, caffeine and its metabolites may be decreased due to malabsorption. These findings are similar to metabolic alterations in iPD. Thus, serum/plasma metabolomics may reflect the association between parkin dysfunction and parkinsonism.

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“…From this study, Burte et al identified 20 metabolites that were statistically-significant for prediction of PD progression and mild cognitive impairment. In another study, Lewitt and colleagues employed dual UPLC/MS/MS and GC-MS analysis of biofluids from PD patients to identify small-molecule biomarkers [7]. From the nontargeted metabolomics analysis, the authors identified 575 and 383 distinct biomarkers from plasma and CSF samples, respectively.…”

Section: Introductionmentioning

confidence: 99%

Integrated use of LC/MS/MS and LC/Q-TOF/MS targeted metabolomics with automated label-free microscopy for quantification of purine metabolites in cultured mammalian cells

Nybo

Lamberts

2018

Preprint

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Purine metabolites have been implicated as clinically relevant biomarkers of worsening or improving Parkinson's disease (PD) progression. However, the identification of purine molecules as biomarkers in PD has largely been determined using non-targeted metabolomics analysis. The primary goal of this study was to develop an economical targeted metabolomics approach for the routine detection of purine molecules in biological samples. Specifically, this project utilized LC/MS/MS and LC/QTOF/MS to accurately quantify levels of six purine molecules in samples from cultured N2a murine neuroblastoma cells. The targeted metabolomics workflow was integrated with automated label-free digital microscopy, which enabled normalization of purine concentration per unit cell in the absence of fluorescent dyes. The established method offered significantly enhanced selectivity compared to previously published procedures. In addition, this study demonstrates that a simple, quantitative targeted metabolomics approach can be developed to identify and quantify purine metabolites in biological samples. We envision that this method could be broadly applicable to quantification of purine metabolites from other complex biological samples, such as cerebrospinal fluid or blood.

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Metabolomic biomarkers as strong correlates of Parkinson disease progression

Abstract: Metabolomic profiling of plasma yielded strong prediction of PD progression and offered biomarkers that may provide new insights into PD pathogenesis.

Cited by 122 publications

References 35 publications

Comment on ‘Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease’ by Hiller et al

Comment on ‘Distinct Metabolomic Signature in Cerebrospinal Fluid in Early Parkinson's Disease’ by Hiller et al

Metabolomics‐based identification of metabolic alterations in PARK2

Integrated use of LC/MS/MS and LC/Q-TOF/MS targeted metabolomics with automated label-free microscopy for quantification of purine metabolites in cultured mammalian cells

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