| 1. |
- Bryan, Thomas, et al.
(författare)
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The robust electrochemical detection of a Parkinson's disease marker in whole blood sera
- 2012
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 3:12, s. 3468-3473
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Tidskriftsartikel (refereegranskat)abstract
- Protein aggregation, leading to amyloid deposition in the brain, is implicated in the pathology of a number of increasingly prevalent neurodegeneration states such as Parkinson's disease (PD), Alzheimer's disease and prion diseases. The body's protective response to the formation of such deposits is to generate specific autoimmune antibodies. Alpha-synuclein, a natively unfolded protein relatively abundant in the brain, is the main constituent of Lewy body amyloid dispositions in PD. Previous assays determining content of alpha-synuclein in bodily fluids have proven to be largely inconclusive. Here we have taken a novel approach in utilising alpha-synuclein modified electrodes to sample the autoantibodies generated as the body responds to changes in its homeostasis. We show that these electroanalytical assays not only robustly distinguish between disease state and control individuals but also map out disease progression with unprecedented sensitivity and clarity. The impedimetric electrode surfaces are highly specific, reusable, exhibit a linear range from 0.5 to 10 nM and a detection limit of 55 +/- 3 pM. We believe electroanalyses such as these, possible with less than 10 microlitres of fluid and a total assay time of only a few minutes, to be of value for early diagnosis of PD and possibly other alpha-synucleinopathies, and for monitoring disease progression and effects of possible disease modifying interventions.
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| 2. |
- Horvath, Istvan, et al.
(författare)
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Immunochemical Detection of alpha-Synuclein Autoantibodies in Parkinson's Disease : Correlation between Plasma and Cerebrospinal Fluid Levels
- 2017
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 8:6, s. 1170-1176
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies to Parkinson's disease (PD) amyloidogenic protein, a-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 a-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 a-synuclein antibodies in both plasma and CSF. For the first time, we showed the correlation between plasma and CSF a-synuclein antibody levels for mild, moderate, and combined PD groups. This indicates the potentiality of a-synuclein antibodies as PD biomarker and the increased diagnostic power of their simultaneous analysis in plasma and CSF.
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| 3. |
- Horvath, Istvan, et al.
(författare)
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Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease
- 2016
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:1, s. 34-39
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Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1-42 and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1-42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1-42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD.
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| 4. |
- Wilhelm, Kristina R, 1976-, et al.
(författare)
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Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients
- 2007
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 14:3, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.
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