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Published in: Neurological Sciences 5/2019

01-05-2019 | Parkinson's Disease | Review Article

Plasma alpha-synuclein levels in patients with Parkinson’s disease: a systematic review and meta-analysis

Authors: Anastasia Bougea, Leonidas Stefanis, George P Paraskevas, Evangelia Emmanouilidou, Kostas Vekrelis, Elisabeth Kapaki

Published in: Neurological Sciences | Issue 5/2019

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Abstract

Objective

To date, there are no definitive biomarkers for diagnose Parkinson’s disease (PD). The detection of α-synuclein (α-Syn) in plasma of PD patients has yielded promising but inconclusive results. To determine the performance of α-Syn as a diagnostic biomarker of PD, we used a meta-analysis.

Methods

We identified 173 studies through a systematic literature review. From those, only studies reporting data on total α-Syn levels were included in the meta-analysis (10 publications, 1302 participants). Quality of studies was assessed by Newcastle-Ottawa scale.

Results

The α-Syn levels were significantly higher in PD patients than healthy controls (standardized mean difference [SMD] = 0.778, 95% confidence interval = 0.284 to 1.272, p = 0.002). Similar results were found after omitting any individual study from meta-analysis, with SMD ranges from 0.318 (95% CI = 0.064 to 0.572, p = 0.014) to 0.914 (95% CI = 0.349 to 1.480, p = 0.002). According to meta-regression analysis, increased mean patients age (slope = − 0.232, 95% CI = − 0.456 to − 0.008, p = 0.042), increased total number of participants (slope = − 0.007, 95% CI = − 0.013 to − 0.0004, p = 0.038), and increased percentage of males (slope = − 6.444, 95% CI = − 10.841 to − 2.047, p = 0.004) were associated with decreased SMD of α-Syn levels across studies. We did not find any significant association between the SMD in α-Syn levels and disease duration, disease severity, and quality of studies. Most of studies applied ELISA assays.

Conclusion

Total plasma α-Syn levels were higher in PD patients than controls. Analytical factors were important limitations.
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Literature
2.
go back to reference Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184CrossRefPubMedPubMedCentral Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184CrossRefPubMedPubMedCentral
3.
go back to reference Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95(11):6469–6473CrossRefPubMedPubMedCentral Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95(11):6469–6473CrossRefPubMedPubMedCentral
8.
go back to reference Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science (New York, NY) 276 (5321):2045–2047 Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science (New York, NY) 276 (5321):2045–2047
9.
go back to reference Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521–533CrossRefPubMed Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521–533CrossRefPubMed
11.
go back to reference Simonsen AH, Kuiperij B, El-Agnaf OM, Engelborghs S, Herukka SK, Parnetti L, Rektorova I, Vanmechelen E, Kapaki E, Verbeek M, Mollenhauer B (2016) The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature. Biomark Med 10(1):19–34. https://doi.org/10.2217/bmm.14.105 CrossRefPubMed Simonsen AH, Kuiperij B, El-Agnaf OM, Engelborghs S, Herukka SK, Parnetti L, Rektorova I, Vanmechelen E, Kapaki E, Verbeek M, Mollenhauer B (2016) The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature. Biomark Med 10(1):19–34. https://​doi.​org/​10.​2217/​bmm.​14.​105 CrossRefPubMed
19.
20.
go back to reference El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J : Off Publ Fed Am Soc Exp Biol 20(3):419–425. https://doi.org/10.1096/fj.03-1449com CrossRef El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J : Off Publ Fed Am Soc Exp Biol 20(3):419–425. https://​doi.​org/​10.​1096/​fj.​03-1449com CrossRef
21.
go back to reference Foulds PG, Mitchell JD, Parker A, Turner R, Green G, Diggle P, Hasegawa M, Taylor M, Mann D, Allsop D (2011) Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease. FASEB J: Off Publ Fed Am Soc Exp Biol 25(12):4127–4137. https://doi.org/10.1096/fj.10-179192 CrossRef Foulds PG, Mitchell JD, Parker A, Turner R, Green G, Diggle P, Hasegawa M, Taylor M, Mann D, Allsop D (2011) Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease. FASEB J: Off Publ Fed Am Soc Exp Biol 25(12):4127–4137. https://​doi.​org/​10.​1096/​fj.​10-179192 CrossRef
26.
go back to reference Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) Movement disorders society scientific issues committee report: SIC task force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord : Off J Mov Disord Soc 18(5):467–486. https://doi.org/10.1002/mds.10459 CrossRef Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) Movement disorders society scientific issues committee report: SIC task force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord : Off J Mov Disord Soc 18(5):467–486. https://​doi.​org/​10.​1002/​mds.​10459 CrossRef
27.
31.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634CrossRef Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634CrossRef
32.
go back to reference Rosenthal R (1979) The file drawer problem and tolerance for null results. Psychol Bull 86(3):638–641CrossRef Rosenthal R (1979) The file drawer problem and tolerance for null results. Psychol Bull 86(3):638–641CrossRef
33.
go back to reference Duval STR (2000) A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc 95(449):89–98 Duval STR (2000) A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc 95(449):89–98
34.
go back to reference Valentine JCPT, Rothstein HR (2010) How many studies do you need? A primer on statistical power for meta-analysis. J Educ Behav Stat 35(2):215–247CrossRef Valentine JCPT, Rothstein HR (2010) How many studies do you need? A primer on statistical power for meta-analysis. J Educ Behav Stat 35(2):215–247CrossRef
36.
go back to reference Sturdivant RXLS, Hosmer DW (2013) Applied logistic regression, 3rd edn. John Wiley & Sons, New Jersey Sturdivant RXLS, Hosmer DW (2013) Applied logistic regression, 3rd edn. John Wiley & Sons, New Jersey
37.
go back to reference Borenstein M HL, Higgins J, Rothstein H. (2005) Comprehensive meta-analysis version 2. Biostat. Englewood, NJ Borenstein M HL, Higgins J, Rothstein H. (2005) Comprehensive meta-analysis version 2. Biostat. Englewood, NJ
44.
go back to reference Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain J Neurol 133(Pt 3):713–726. https://doi.org/10.1093/brain/awq008 CrossRef Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain J Neurol 133(Pt 3):713–726. https://​doi.​org/​10.​1093/​brain/​awq008 CrossRef
Metadata
Title
Plasma alpha-synuclein levels in patients with Parkinson’s disease: a systematic review and meta-analysis
Authors
Anastasia Bougea
Leonidas Stefanis
George P Paraskevas
Evangelia Emmanouilidou
Kostas Vekrelis
Elisabeth Kapaki
Publication date
01-05-2019
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 5/2019
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-019-03738-1

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