Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease |
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Authors: | Tokuda Takahiko Salem Sultan A Allsop David Mizuno Toshiki Nakagawa Masanori Qureshi Mohamed M Locascio Joseph J Schlossmacher Michael G El-Agnaf Omar M A |
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Institution: | Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan, and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA. |
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Abstract: | There is ample biochemical, pathological, and genetic evidence that the metabolism of alpha-synuclein (alpha-syn) plays a crucial role in the pathogenesis of Parkinson disease (PD). To examine whether quantification of alpha-syn in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of PD, we developed a specific ELISA system and measured the concentration of alpha-syn in CSF from 33 patients with PD (diagnosed according to UK PD Society Brain Bank criteria) and 38 control subjects including 9 neurologically healthy individuals. We found that PD patients had significantly lower alpha-syn levels in their CSF than the control groups (p<0.0001) even after adjusting for gender and age. Age was independently associated with lower alpha-syn levels. Logistic regression analysis showed that reduction in CSF alpha-syn served as a significant predictor of PD beyond age and gender alone (area under ROC curve, c=0.882). Furthermore, we observed a close inverse correlation between alpha-syn levels in CSF and assigned Hoehn and Yahr score in this cohort of 71 living subjects (p<0.0001), even after adjusting for age. These findings identify in the quantification of alpha-syn from CSF a potential laboratory marker to aid the clinical diagnosis of PD. |
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Keywords: | Parkinson disease Neurodegenerative diseases α-Synuclein Cerebrospinal fluid ELISA Biomarker Diagnosis |
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