scholarly journals The Diagnostic and Differential Diagnosis Utility of Cerebrospinal Fluidα-Synuclein Levels in Parkinson’s Disease: A Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bo Zhou ◽  
Min Wen ◽  
Wen-Feng Yu ◽  
Chun-Lin Zhang ◽  
Ling Jiao

Several recent studies showed thatα-syn might be a potential diagnostic biomarker for PD in human cerebrospinal fluid (CSF), but the results were inconsistent. The purpose of this meta-analysis was to investigate the diagnostic and differential diagnosis efficacy of CSFα-syn in PD. Studies which measured CSFα-syn orα-syn oligomers in patients with PD and met the inclusion criteria were included in the analysis. Results of the meta-analysis indicated that mean concentration of CSFα-syn was significantly lower in PD compared to controls and significantly higher in PD compared to multiple system atrophy (MSA). No significant difference in mean concentration of CSFα-syn was found between PD and dementia with Lewy bodies (DLB). Mean concentration of CSFα-syn was slightly decreased in PD compared to progressive supranuclear palsy (PSP). Mean concentration of CSFα-syn oligomers was significantly higher in PD than control. These results support the findings that CSFα-syn may be a potential diagnostic and differential diagnosis biomarker in PD compared to control and MSA but not DLB. Furthermore,α-syn oligomer may represent a better biomarker for diagnosis of PD.

2020 ◽  
Author(s):  
Olivier BOUSIGES ◽  
Nathalie Philippi ◽  
Thomas Lavaux ◽  
Armand Perret-Liaudet ◽  
Ingolf Lachmann ◽  
...  

Abstract Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Furthermore, alpha-synuclein levels were elevated not only in AD patients with a typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also in AD patients with an atypical “Alzheimer” profile (i.e. one or no pathological biomarkers).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarkers.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)


2015 ◽  
Vol 27 (9) ◽  
pp. 1429-1438 ◽  
Author(s):  
Zheng-Yu Wang ◽  
Zhen-Min Han ◽  
Qi-Fei Liu ◽  
Wei Tang ◽  
Kui Ye ◽  
...  

ABSTRACTBackground:The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA).Methods:A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models.Results:CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (−0.21, 0.24), z = 0.13, P = 0.894].Conclusions:Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.


2020 ◽  
Author(s):  
Takayuki Katayama ◽  
Jun Sawada ◽  
Kae Takahashi ◽  
Osamu Yahara ◽  
Naoyuki Hasebe

Abstract Background: To investigate the usefulness of cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels as a candidate biomarker of neurodegeneration in Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).Methods: We performed a systematic search of PubMed, the Cochrane Library, SCOPUS, and Google Scholar to find studies that investigated the CSF levels of NSE in AD, PD, DLB, and/or MSA. For each disease, we pooled all available data and performed a meta-analysis, and meta-regression analyses of age and sex were conducted when significant in the main analysis.Results: Twenty studies were included (13 for AD, 8 for PD/PDD/DLB, and 4 for MSA). Significantly elevated CSF NSE levels were detected in AD (Hedges’ g = 0.822, 95% confidence interval [95%CI]: 0.332 to 1.311, p = 0.0010), but the data exhibited high heterogeneity (I2 = 88.43%, p<0.001). The meta-regression analysis of AD showed that age (p<0.001), but not sex, had a significant effect on NSE. A meta-analysis of all the pooled data for PD/PDD/DLB did not show any significant changes in the CSF NSE level, but a sub-group analysis of PDD/DLB revealed significantly elevated CSF NSE levels (Hedges’ g = 0.507, 95%CI: 0.020 to 0.993, p = 0.0412). No significant changes in CSF NSE levels were detected in MSA.Conclusions: This study provided evidence about the usefulness of CSF NSE levels as a biomarker in AD and PDD/DLB, and age was found to affect the CSF NSE levels of AD patients.


2020 ◽  
Author(s):  
Olivier BOUSIGES ◽  
Nathalie Philippi ◽  
Thomas Lavaux ◽  
Armand Perret-Liaudet ◽  
Ingolf Lachmann ◽  
...  

Abstract Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB.Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer’s biomarker does not improve the differential diagnosis between AD and DLB.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)


2020 ◽  
Author(s):  
Olivier BOUSIGES ◽  
Nathalie Philippi ◽  
Thomas Lavaux ◽  
Armand Perret-Liaudet ◽  
Ingolf Lachmann ◽  
...  

Abstract Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB.Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer’s biomarker does not improve the differential diagnosis between AD and DLB.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)


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