Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of <scp>l</scp>‐<scp>DOPA</scp> treatment and changes in levodopa‐induced dyskinesia

Andersen, Andreas Dammann; Blaabjerg, Morten; Binzer, Michael; Kamal, Akram; Thagesen, Helle; Kjær, Troels W.; Stenager, Egon; Gramsbergen, Jan Bert

doi:10.1111/jnc.13997

Cited by 38 publications

(37 citation statements)

References 59 publications

(67 reference statements)

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“…In this respect, it is clear that the extent of the dopaminergic disturbance is most evident in PD, with severely decreased CSF DOPAC and DA concentrations compared to CONTR. This finding of lowered CSF DOPAC and DA concentrations in PD are supported by several other studies [40,41], even though the sample sizes of these studies were rather small (n = 4 and n = 7, respectively). It is interesting to note that we did not find decreased DA concentrations in FTD or ALS, possibly reflecting a distinct disease mechanism from PD.…”

Section: Discussionsupporting

confidence: 77%

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

et al. 2020

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Exploring the neurochemical continuum between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with respect to monoamines and kynurenines in cerebrospinal fluid (CSF) and serum, may be useful to identify possible new research/therapeutic targets. Hence, we analysed monoamines and kynurenines in CSF and serum derived from patients with FTD (n = 39), ALS (n = 23), FTD-ALS (n = 4) and age-matched control subjects (n = 26), using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) with electrochemical detection (ECD) and liquid chromatography tandem mass spectrometry, respectively. We noted a shared dopaminergic disturbance in FTD and ALS when compared to CONTR, with significantly increased serum DA levels and decreased DOPAC concentrations, as well as decreased DOPAC/DA ratios in both disease groups. In CSF, significantly reduced DOPAC concentrations in FTD and ALS were observed as well. Here, a significant increase in DA levels and decrease in DOPAC/DA ratios was only found in FTD relative to CONTR. With respect to the kynurenine pathway (KP), we only found decreased HK/XA ratios, indicative for vitamin B6 status, in serum of ALS subjects compared to FTD. The dopaminergic commonalities observed in FTD and ALS might relate to a disturbance of dopaminergic nerve terminals in projection areas of the substantia nigra and/or ventral tegmental area, although these findings should first be confirmed in brain tissue. Lastly, based on the results of this work, the KP does not hold promise as a research/therapeutic target in FTD and ALS.

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Section: Discussionsupporting

confidence: 77%

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

et al. 2020

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“…In Table S1, patient data are summarized for CSF samples. Further clinical details of patients and controls can be found in Andersen et al (2017). All PD patients and controls were informed in writing and orally about the project, and gave written consent prior to participation.…”

Section: Methodsmentioning

confidence: 99%

“…Both pre-synaptic and post-synaptic maladaptive changes contribute to the pathophysiology of LID (Bastide et al 2015;De Deurwaerdere et al 2017). Recently, we reported elevated dopamine (DA)/L-DOPA and reduced dihydroxyphenyl acetic acid/DA ratios in CSF of LID patients as compared to nondyskinetic PD patients receiving L-DOPA, suggesting increased DA release from non-DA cells and deficient DA re-uptake in PD-LID patients (Andersen et al 2017). In addition to uncontrolled dopamine release acting on supersensitive D1 receptors, enhanced glutamatergic signaling may contribute to LID.…”

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confidence: 99%

Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia

Havelund

Andersen

Binzer

et al. 2017

Journal of Neurochemistry

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L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia.

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“…For original articles on catecholamines and metabolites as biomarkers in PD, we refer to [ 29 , 30 , 31 ] and for recent reviews [ 32 , 33 , 34 ]. Loss of catecholamines and their metabolites in PD biofluids can only reliably be detected in drug-naive patients or after long-term drug (L-DOPA) wash-out.…”

Section: Metabolites As Biomarkersmentioning

confidence: 99%

“…Loss of catecholamines and their metabolites in PD biofluids can only reliably be detected in drug-naive patients or after long-term drug (L-DOPA) wash-out. Furthermore, CSF levels of the dopamine (DA) metabolite homovanillic acid (HVA) appear to be a less reliable marker for loss of central DA than CSF levels of the other DA metabolite, dihydroxyphenylacetic acid (DOPAC), which shows high accuracy in separating PD patients, including recently-diagnosed patients, from controls [ 29 , 30 , 31 ].…”

Section: Metabolites As Biomarkersmentioning

confidence: 99%

Biomarker Research in Parkinson’s Disease Using Metabolite Profiling

et al. 2017

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Biomarker research in Parkinson’s disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifactorial disease, which requires a more precise diagnosis and personalized medication to obtain optimal outcome. In recent years, advanced metabolite profiling of body fluids like serum/plasma, CSF or urine, known as “metabolomics”, has become a powerful and promising tool to identify novel biomarkers or “metabolic fingerprints” characteristic for PD at various stages of disease. In this review, we discuss metabolite profiling in clinical and experimental PD. We briefly review the use of different analytical platforms and methodologies and discuss the obtained results, the involved metabolic pathways, the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD.

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Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l‐DOPA treatment and changes in levodopa‐induced dyskinesia

Cited by 38 publications

References 59 publications

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia

Biomarker Research in Parkinson’s Disease Using Metabolite Profiling

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