Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease.
BACKGROUND
To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology.


METHODS
We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory.


RESULTS
The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05).


CONCLUSIONS
Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.
Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Tokuda
M M
MM
Qureshi
M T
MT
Ardah
S
S
Varghese
S A S
SA
Shehab
T
T
Kasai
N
N
Ishigami
A
A
Tamaoka
M
M
Nakagawa
O M A
OM
El-Agnaf
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000737:chemistry; D001923:Brain Chemistry; D015331:Cohort Studies; D003430:Cross-Sectional Studies / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000378:metabolism; D010865:Pilot Projects; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid* / Q000737:chemistry
D015415:Biomarkers; D051844:alpha-Synuclein