Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease

T. Tokuda, M. M. Qureshi, M. T. Ardah, S. Varghese, S. A.S. Shehab, T. Kasai, N. Ishigami, A. Tamaoka, M. Nakagawa, Omar Ali El-Agnaf

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Abstract

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). Conclusion: 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.

Original languageEnglish
Pages (from-to)1766-1772
Number of pages7
JournalNeurology
Volume75
Issue number20
DOIs
Publication statusPublished - 16 Nov 2010
Externally publishedYes

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Synucleins
Parkinson Disease
Area Under Curve
Progressive Supranuclear Palsy
Alzheimer Disease
Parkinsonian Disorders
Nonparametric Statistics
Routine Diagnostic Tests
ROC Curve
Early Diagnosis
Cross-Sectional Studies

ASJC Scopus subject areas

  • Clinical Neurology

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Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. / Tokuda, T.; Qureshi, M. M.; Ardah, M. T.; Varghese, S.; Shehab, S. A.S.; Kasai, T.; Ishigami, N.; Tamaoka, A.; Nakagawa, M.; Ali El-Agnaf, Omar.

In: Neurology, Vol. 75, No. 20, 16.11.2010, p. 1766-1772.

Research output: Contribution to journalArticle

Tokuda, T, Qureshi, MM, Ardah, MT, Varghese, S, Shehab, SAS, Kasai, T, Ishigami, N, Tamaoka, A, Nakagawa, M & Ali El-Agnaf, O 2010, 'Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease', Neurology, vol. 75, no. 20, pp. 1766-1772. https://doi.org/10.1212/WNL.0b013e3181fd613b
Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SAS, Kasai T et al. Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology. 2010 Nov 16;75(20):1766-1772. https://doi.org/10.1212/WNL.0b013e3181fd613b
Tokuda, T. ; Qureshi, M. M. ; Ardah, M. T. ; Varghese, S. ; Shehab, S. A.S. ; Kasai, T. ; Ishigami, N. ; Tamaoka, A. ; Nakagawa, M. ; Ali El-Agnaf, Omar. / Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. In: Neurology. 2010 ; Vol. 75, No. 20. pp. 1766-1772.
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abstract = "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). Conclusion: 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.",
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AU - Tokuda, T.

AU - Qureshi, M. M.

AU - Ardah, M. T.

AU - Varghese, S.

AU - Shehab, S. A.S.

AU - Kasai, T.

AU - Ishigami, N.

AU - Tamaoka, A.

AU - Nakagawa, M.

AU - Ali El-Agnaf, Omar

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N2 - 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). Conclusion: 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.

AB - 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). Conclusion: 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.

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