scholarly journals Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1429-1442
Author(s):  
Marianne von Euler Chelpin ◽  
Linda Söderberg ◽  
Johanna Fälting ◽  
Christer Möller ◽  
Marco Giorgetti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Corticobasal Degeneration ◽  
Alpha Synuclein ◽  
Cross Reactivity ◽  
Potential Biomarker ◽  
Csf Levels

Background: Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. Objective: To develop a novel method to quantify cerebrospinal fluid (CSF) levels of α-synuclein protofibrils (α-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. Methods: A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer’s disease (AD, tau<350 pg/mL, amyloid-beta 42 (Aβ42)>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total α-synuclein (α-syn) levels were analyzed with a commercial ELISA-kit. Results: The assay is specific to α-syn PF, with no cross-reactivity to monomeric α-syn, or the β- and γ-synuclein variants. CSF α-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using α-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total α-syn were significantly different between the PD and CBD groups (p = 0.04). Conclusion: The developed method specifically quantifies α-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.

scholarly journals Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Xu-Ying Li ◽  
Wei Li ◽  
Xin Li ◽  
Xu-Ran Li ◽  
Linjuan Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Late Onset ◽  
Area Under The Curve ◽  
Alpha Synuclein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Olfactory Loss ◽  
Potential Biomarker

Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-α-syn (pS-α-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (p = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (p = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (p = 0.012) and olfactory loss (p = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp; Yahr stages (H&amp;Y) (p for trend =0.02 and &lt;0.001) as well as UPDRS III (R2 = 0.031, p = 0.0042) and MoCA scores (R2 = 0.048, p = 0.0004). The results obtained suggest that pS-α-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.

scholarly journals Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

2018 ◽  
Vol 8 (4) ◽  
pp. 52 ◽  
Author(s):  
Manuel Menéndez-González ◽  
Huber Padilla-Zambrano ◽  
Cristina Tomás-Zapico ◽  
Benjamin García
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Therapeutic Strategy ◽  
Alpha Synuclein

scholarly journals Single Molecule FRET Characterization of Oligomers from Alpha-Synuclein Early Onset Parkinson's Disease Mutants

2014 ◽  
Vol 106 (2) ◽  
pp. 269a ◽  
Author(s):  
Laura Tosatto ◽  
Mathew H. Horrocks ◽  
Cremades Nunilo ◽  
Tim Guilliams ◽  
Mauro Dalla Serra ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Molecule ◽  
Early Onset ◽  
Alpha Synuclein ◽  
Single Molecule Fret ◽  
Early Onset Parkinson’S Disease

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in Parkinson’s disease and atypical parkinsonian syndromes

2021 ◽  
Author(s):  
Michaela Kaiserova ◽  
Monika Chudackova ◽  
Hana Prikrylova Vranova ◽  
Katerina Mensikova ◽  
Anetta Kastelikova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Statistical Significance ◽  
Corticobasal Degeneration ◽  
Control Group ◽  
Csf Biomarkers ◽  
Parkinsonian Syndromes ◽  
Significant Difference ◽  
Hydroxyindoleacetic Acid

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).

scholarly journals Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson’s disease genetically related mutants

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Laura Tosatto ◽  
Mathew H. Horrocks ◽  
Alexander J. Dear ◽  
Tuomas P. J. Knowles ◽  
Mauro Dalla Serra ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Molecule ◽  
Alpha Synuclein ◽  
Single Molecule Fret

scholarly journals Endogenous α-SYN protein analysis from human brain tissues using single-molecule pull-down assay

2017 ◽  
Author(s):  
Goun Je ◽  
Benjamin Croop ◽  
Sambuddha Basu ◽  
Jialei Tang ◽  
Kyu Young Han ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Brain ◽  
Single Molecule ◽  
Alpha Synuclein ◽  
Postmortem Brains ◽  
Diagnostic Applications ◽  
Reliable Methods ◽  
Molecular Nature

AbstractAlpha-synuclein (α-SYN) is a central molecule in Parkinson’s disease pathogenesis. Despite several studies, the molecular nature of endogenous α-SYN especially in human brain samples is still not well understood due to the lack of reliable methods and the limited amount of bio-specimens. Here, we introduce α-SYN single-molecule pull-down (α-SYN SiMPull) assay combined with in vivo protein crosslinking to count individual α-SYN protein and assess its native oligomerization states from biological samples including human postmortem brains. This powerful single-molecule assay can be highly useful in diagnostic applications using various specimens for neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease.

scholarly journals Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A): Could It Be a Promising Biomarker and Therapeutic Target in Parkinson’s Disease?

2022 ◽  
Author(s):  
Sijia Yin ◽  
Chao Han ◽  
Yun Xia ◽  
Fang Wan ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Phosphatase ◽  
Essential Role ◽  
Protein Phosphatase 2A ◽  
Area Under The Curve ◽  
Alpha Synuclein ◽  
Phosphatase 2A ◽  
Induced Aggregation ◽  
Age And Sex

AbstractParkinson’s disease (PD) is an incurable neurodegenerative disease characterized by aggregation of pathological alpha-synuclein (α-syn) and loss of dopaminergic neuron in the substantia nigra. Inhibition of phosphorylation of the α-syn has been shown to mediate alleviation of PD-related pathology. Protein phosphatase 2A (PP2A), an important serine/threonine phosphatase, plays an essential role in catalyzing dephosphorylation of the α-syn. Here, we identified and validated cancerous inhibitor of PP2A (CIP2A), as a potential diagnostic biomarker for PD. Our data showed that plasma CIP2A concentrations in PD patients were significantly lower compared to age- and sex-matched controls, 1.721 (1.435–2.428) ng/ml vs 3.051(2.36–5.475) ng/ml, p < 0.0001. The area under the curve of the plasma CIP2A in distinguishing PD from the age- and sex-matched controls was 0.776. In addition, we evaluated the role of CIP2A in PD-related pathogenesis in PD cellular and MPTP-induced mouse model. The results demonstrated that CIP2A is upregulated in PD cellular and MPTP-induced mouse models. Besides, suppression of the CIP2A expression alleviates rotenone induced aggregation of the α-syn as well as phosphorylation of the α-syn in SH-SY5Y cells, which is associated with increased PP2A activity. Taken together, our data demonstrated that CIP2A plays an essential role in the mechanisms related to PD development and might be a novel PD biomarker.

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