Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease.
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.
Tokuda
Takahiko
T
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.
Salem
Sultan A
SA
Allsop
David
D
Mizuno
Toshiki
T
Nakagawa
Masanori
M
Qureshi
Mohamed M
MM
Locascio
Joseph J
JJ
Schlossmacher
Michael G
MG
El-Agnaf
Omar M A
OM
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*
D051844:alpha-Synuclein