title: Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease.
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.
authors.affiliation: 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.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.forename: Sultan A
authors.initials: SA
authors.lastname: Salem
authors.forename: David
authors.initials: D
authors.lastname: Allsop
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Qureshi
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schlossmacher
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D012737:Sex Factors; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D051844:alpha-Synuclein