Serveur d'exploration sur la maladie de Parkinson

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DJ-1 and -synuclein in human cerebrospinal fluid as biomarkers of Parkinsons disease

Identifieur interne : 000475 ( Main/Exploration ); précédent : 000474; suivant : 000476

DJ-1 and -synuclein in human cerebrospinal fluid as biomarkers of Parkinsons disease

Auteurs : Zhen Hong [États-Unis, République populaire de Chine] ; Min Shi [États-Unis] ; Kathryn A. Chung [États-Unis] ; Joseph F. Quinn [États-Unis] ; Elaine R. Peskind [États-Unis] ; Douglas Galasko [États-Unis] ; Joseph Jankovic [États-Unis] ; Cyrus P. Zabetian [États-Unis] ; James B. Leverenz [États-Unis] ; Geoffrey Baird [États-Unis] ; Thomas J. Montine [États-Unis] ; Aneeka M. Hancock [États-Unis] ; Hyejin Hwang [États-Unis] ; Catherine Pan [États-Unis] ; Joshua Bradner [États-Unis] ; Un J. Kang [États-Unis] ; Poul H. Jensen [Danemark] ; Jing Zhang [États-Unis]

Source :

RBID : ISTEX:49E5A3FDBFB0A647597C89EAED71532F0863A855

Abstract

Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinsons disease. Both DJ-1 and -synuclein, two proteins critically involved in Parkinsons disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and -synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and -synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and -synuclein from 117 patients with Parkinsons disease, 132 healthy individuals and 50 patients with Alzheimers disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and -synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and -synuclein levels were decreased in Parkinsons patients versus controls or Alzheimers patients when blood contamination was controlled for. In the population aged 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and -synuclein, respectively, the sensitivity and specificity for patients with Parkinsons disease versus controls were 90 and 70 for DJ-1, and 92 and 58 for -synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or -synuclein and the severity of Parkinsons disease. Taken together, this represents the largest scale study for DJ-1 or -synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and -synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinsons disease, if variables such as blood contamination and age are taken into consideration.

Url:
DOI: 10.1093/brain/awq008


Affiliations:


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Le document en format XML

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<div type="abstract">Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinsons disease. Both DJ-1 and -synuclein, two proteins critically involved in Parkinsons disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and -synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and -synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and -synuclein from 117 patients with Parkinsons disease, 132 healthy individuals and 50 patients with Alzheimers disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and -synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and -synuclein levels were decreased in Parkinsons patients versus controls or Alzheimers patients when blood contamination was controlled for. In the population aged 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and -synuclein, respectively, the sensitivity and specificity for patients with Parkinsons disease versus controls were 90 and 70 for DJ-1, and 92 and 58 for -synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or -synuclein and the severity of Parkinsons disease. Taken together, this represents the largest scale study for DJ-1 or -synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and -synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinsons disease, if variables such as blood contamination and age are taken into consideration.</div>
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<name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul H." last="Jensen">Poul H. Jensen</name>
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