Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease

• Published in: Biochemical and biophysical research communications Vol. 349; no. 1; pp. 162 - 166
• Main 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.10.2006
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Aging; alpha-Synuclein - cerebrospinal fluid; Biomarker; Case-Control Studies; Cerebrospinal fluid; Diagnosis; ELISA; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Neurodegenerative diseases; Parkinson disease; Parkinson Disease - cerebrospinal fluid; Parkinson Disease - diagnosis; Sex Factors; α-Synuclein; α-Synuclein; Biomarker; Neurodegenerative diseases; Parkinson disease; Cerebrospinal fluid; Diagnosis; ELISA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.08.024

There is ample biochemical, pathological, and genetic evidence that the metabolism of α-synuclein (α-syn) plays a crucial role in the pathogenesis of Parkinson disease (PD). To examine whether quantification of α-syn in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of PD, we developed a specific ELISA system and measured the concentration of α-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 α-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 α-syn levels. Logistic regression analysis showed that reduction in CSF α-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 α-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 α-syn from CSF a potential laboratory marker to aid the clinical diagnosis of PD.