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Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects.

ABSTRACT: Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases.We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1·5-fold or greater difference in volume between PD patients and controls were excised from the two-dimensional gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods.Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1, and glutathione-S-transferase-Pi, were found to be different between PD and NC populations.These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.

SUBMITTER: Maarouf CL

PROVIDER: S-EPMC3681206 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects.

Maarouf Chera L CL Beach Thomas G TG Adler Charles H CH Shill Holly A HA Sabbagh Marwan N MN Wu Terence T Walker Douglas G DG Kokjohn Tyler A TA Roher Alex E AE

Neurological research 20120901 7

<h4>Objectives</h4>Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases.<h4>Methods</h4>We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference g ...[more]

PMID: 22889670

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Project description:Central catecholamine deficiency characterizes ?-synucleinopathies such as Parkinson's disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson's disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects-108 synucleinopathy patients (34 Parkinson's disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson's disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86?±?0.09 (SEM), 1.00?±?0.09, 1.32?±?0.12?nmol/l] than controls (2.15?±?0.18?nmol/l; P?<?0.0001; P?<?0.0001; P?=?0.0002). Dihydroxyphenylglycol was also lower in the three synucleinopathies (8.82?±?0.44, 7.75?±?0.42, 5.82?±?0.65?nmol/l) than controls (11.0?±?0.62?nmol/l; P?=?0.009, P?<?0.0001, P?<?0.0001). Dihydroxyphenylacetic acid was lower and dihydroxyphenylglycol higher in Parkinson's disease than in pure autonomic failure. Dihydroxyphenylacetic acid was 100% sensitive at 89% specificity in separating patients with recent onset of parkinsonism from controls but was of no value in differentiating Parkinson's disease from multiple system atrophy. Synucleinopathies feature cerebrospinal fluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson's disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinal fluid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early Parkinson's disease.

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Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects.

Publications

Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects.

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