An impedimetric assay of α-synuclein autoantibodies in early stage Parkinson's disease (original) (raw)
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ACS chemical neuroscience, 2017
Autoantibodies to Parkinson's disease (PD) amyloidogenic protein, α-synuclein, were recognized as a prospective biomarker for early disease diagnostics, yet there is inconsistency in previous reports, potentially related to PD status. Therefore, plasma and cerebrospinal fluid (CSF) of the cross-sectional cohort of 60 individuals, including recently diagnosed PD patients with mild and moderate PD and age-matched controls, were examined by enzyme-linked immunosorbent assay (ELISA). Nonparametric statistics was used for data analysis. We found significantly elevated levels of α-synuclein autoantibodies in both plasma and CSF in mild PD compared to controls, followed by some decrease in moderate PD. Receiver operating characteristic and effect size analyses confirmed the diagnostic power of α-synuclein antibodies in both plasma and CSF. For the first time, we showed the correlation between plasma and CSF α-synuclein antibody levels for mild, moderate, and combined PD groups. This in...
Frontiers in neurology, 2017
Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson's disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against α-synuclein (α-syn), which is an important protein involved in the pathogenesis of PD. In our study patients with PD (46 patients), Alzheimer's disease (AD) (27 patients) and healthy controls (20 patients) were evaluated according to their sera α-syn AIAs levels. Interestingly, α-syn AIAs were significantly elevated in PD group compared to AD and healthy controls, which advocates their use for diagnosis of PD.
Journal of neurochemistry, 2018
Biomarkers for α-synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD). Endogenous auto-antibodies to α-synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto-antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto-antibodies to α-synuclein could be diagnostic for PD and explain its clinical heterogeneity. To test this hypothesis, we developed an enzyme-linked immunosorbent assay for measuring α-synuclein auto-antibodies in human samples. We evaluated 69 serum samples (16 healthy controls (HC) and 53 PD patients) and 145 CSF samples (52 HC and 93 PD patients) from our Institution. Both serum and CSF were available for 24 participants. Males had higher auto-antibody levels than females in both fluids. CSF auto-antibody levels were significantly higher in PD patients as compared to HC, whereas serum levels were not significantly different. CSF auto-antibody levels did n...
Autoantibodies to alpha-synuclein in inherited Parkinson’s disease
Journal of Neurochemistry, 2006
Neurodegeneration in Parkinson's disease (PD) is accompanied by a local immune reaction in the affected brain regions. It is well established that α-synuclein is directly implicated in the pathogenesis of PD. Development of the disease is often associated with changes of expression and cellular compartmentalisation of this protein; moreover, its oligomers or protofibrils are often released to the CSF and plasma of patients. Aggregated α-synuclein can trigger the activation of microglia; however, its capacity to induce production of specific autoantibodies (AAb) has not been assessed. In this study, we examined the presence of AAb against synuclein family members in the peripheral blood serum of PD patients and control individuals. Presence of AAb against βsynuclein or γ-synuclein showed no association with PD. Multi-epitopic AAb against α-synuclein were detected in 65% of all patients tested and their presence strongly correlated with an inherited mode of the disease but not with other disease-related factors. The frequency of the presence of AAb in the studied group of patients with sporadic form of PD was not significantly different from the frequency in the control group but very high proportion (90%) of patients with familial form of the disease were positive for AAb against α-synuclein. We hypothesise that these AAb could be involved in pathogenesis of the inherited form of PD.
Plasma α-synuclein is decreased in subjects with Parkinson's disease
Experimental Neurology, 2007
α-Synuclein (αSN) is implicated in Parkinson's disease (PD) and is the major component of Lewy bodies (LBs). Although αSN is mainly expressed in neuronal cells and exists as a cytoplasmic protein, it has been found in body fluids including cerebrospinal fluid and blood. This study explored plasma αSN as a diagnostic marker for PD. Western blot analysis was used to characterize plasma αSN compared to brain αSN. Plasma αSN of 16 kDa migrates with the same mobility as its brain counterpart and recombinant αSN on denatured polyacrylamide gels and reacted with three different antibodies against the C-terminal and NAC regions of the αSN protein. The αSN levels in plasma from PD subjects are significantly lower than that in age-matched controls (p = 0.001), and the αSN levels in patients with early-onset PD are lower than that in both late-onset PD and controls. This initial study indicates that measurement of αSN in plasma can provide support for a clinical diagnosis of Parkinson's disease and warrants further study in a larger population.
Biomarkers and the Role of α-Synuclein in Parkinson’s Disease
Frontiers in Aging Neuroscience, 2021
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the presence of α-synuclein (α-Syn)-rich Lewy bodies (LBs) and the preferential loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc). However, the widespread involvement of other central nervous systems (CNS) structures and peripheral tissues is now widely documented. The onset of the molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD, so early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients. Because the clinical diagnosis of PD is challenging, misdiagnosis is common, which highlights the need for disease-specific and early-stage biomarkers. This review article aims to summarize useful biomarkers for the diagnosis of PD, as well as the biomarkers used to monitor disease progression. This review article describes the role of α-Syn in...
PLoS ONE, 2011
Background: Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson's (PD) and Alzheimer's diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer's disease and potentially other neurodegeneration ailments.
The FASEB journal, 2006
To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analysis of blood or cerebrospinal fluid (CSF). ␣-Synuclein (␣-syn) protein has been linked to the pathogenesis of PD with the discovery of mutations in the gene encoding ␣-syn in familial cases with early-onset PD. Lewy bodies and Lewy neurites, which constitute the main pathological features in the brains of patients with sporadic PD and dementia with Lewy bodies, are formed by the conversion of soluble monomers of ␣-syn into insoluble aggregates. We recently reported the presence of ␣-syn in normal human blood plasma and in postmortem CSF. Here, we investigated whether ␣-syn can be used as a biomarker for PD. We have developed a novel ELISA method that detects only oligomeric "soluble aggregates" of ␣-syn. Using this ELISA, we report the presence of significantly elevated
The FASEB Journal, 2006
To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analysis of blood or cerebrospinal fluid (CSF). ␣-Synuclein (␣-syn) protein has been linked to the pathogenesis of PD with the discovery of mutations in the gene encoding ␣-syn in familial cases with early-onset PD. Lewy bodies and Lewy neurites, which constitute the main pathological features in the brains of patients with sporadic PD and dementia with Lewy bodies, are formed by the conversion of soluble monomers of ␣-syn into insoluble aggregates. We recently reported the presence of ␣-syn in normal human blood plasma and in postmortem CSF. Here, we investigated whether ␣-syn can be used as a biomarker for PD. We have developed a novel ELISA method that detects only oligomeric "soluble aggregates" of ␣-syn. Using this ELISA, we report the presence of significantly elevated (P)200.0؍ levels of oligomeric forms of ␣-syn in plasma samples obtained from 34 PD patients compared with 27 controls; 52% (95% confidence intervals 0.353-0.687) of the PD patients displayed signals >0.5 OD with our ELISA assay in comparison to only 14.8% (95% confidence intervals 0.014-0.281) for the control cases. An analysis of the test's diagnostic value revealed a specificity of 0.852 (95% confidence intervals 0.662-0.958), sensitivity of 0.529 (95% confidence intervals 0.351-0.702) and a positive predictive value of 0.818 (95% confidence intervals 0.597-0.948). These observations offer new opportunities for developing diagnostic tests for PD and related diseases and for testing therapeutic agents aimed at preventing or reversing the aggregation of ␣-syn.-El-Agnaf, O. M. A., Salem, S. A.,