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 & Yahr stages (H&Y) (p for trend =0.02 and <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 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 Preliminary Findings on Proline-Rich Protein 14 as a Diagnostic Biomarker for Parkinson’s Disease

2020 ◽  
Author(s):  
Tao Jin ◽  
Xuling Tan ◽  
Xiaoliu Shi ◽  
Lingling Lv ◽  
Xinke Peng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Area Under The Curve ◽  
Morphological Alteration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Potential Biomarker ◽  
Age And Sex ◽  
Proline Rich Protein

Abstract The nuclear envelope component proline-rich protein 14 (PRR14) is involved in the nuclear morphological alteration and activation of the mTOR (mammalian target of rapamycin) signaling pathway, and has been repeatedly shown to be upregulated in patients with Parkinson’s disease (PD). The aim of this study was to explore whether PRR14 can be used as a potential biomarker for the diagnosis of PD. We compared PRR14 expression in PD patients and normal controls in gene expression omnibus (GEO) data. Quantitative enzyme-linked immunosorbent assay (ELISA) was used to detect PRR14 expression in PD patients and age- and sex-matched controls. The relationship between serum PRR14 and clinical phenotype was evaluated using correlation analysis and logistic regression. The expression of PRR14 in whole blood, substantia nigra, and medial substantia nigra was significantly higher in PD patients than in the healthy control group. Compared to plasma, serum was more suitable for the detection of PRR14. Furthermore, serum PRR14 level in PD patients was significantly higher than that in age- and sex-matched controls. The area under the curve for serum PRR14 level in the ability to identify PD versus age- and sex-matched controls was 0.786. In addition, serum PRR14 level was found to correlate with constipation in PD patients. Our findings demonstrate for the first time that serum PRR14 is a potential biomarker for PD.

scholarly journals Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson’s disease: A Preliminary Study

2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Apolipoprotein E ◽  
Pharmacological Intervention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease States ◽  
Disease Spectrum ◽  
Potential Biomarker ◽  
Schizophrenic Patients ◽  
The Right

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.

scholarly journals Diffusion Kurtosis Imaging of Substantia Nigra Is a Sensitive Method for Early Diagnosis and Disease Evaluation in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Guohua Zhang ◽  
Yuhu Zhang ◽  
Chengguo Zhang ◽  
Yukai Wang ◽  
Guixian Ma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Rating Scale ◽  
Diffusion Tensor ◽  
Diffusion Kurtosis Imaging ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Diffusion Kurtosis ◽  
Sensitive Method

Background.To diagnose Parkinson disease (PD) in an early stage and accurately evaluate severity, it is important to develop a sensitive method for detecting structural changes in the substantia nigra (SN).Method.Seventy-two untreated patients with early PD and 72 healthy controls underwent diffusion tensor and diffusion kurtosis imaging. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Mean kurtosis (MK) and fractional anisotropy in the SN were compared between the groups. Receiver operating characteristic (ROC) and Spearman correlation analyses were used to compare the diagnostic accuracy and correlate imaging findings with Hoehn-Yahr (H-Y) staging and part III of the Unified Parkinson’s Disease Rating Scale (UPDRS-III).Result.MK in the SN was increased significantly in PD patients compared with healthy controls. The area under the ROC curve was 0.976 for MK in the SN (sensitivity, 0.944; specificity, 0.917). MK in the SN had a positive correlation with H-Y staging and UPDRS-III scores.Conclusion.Diffusion kurtosis imaging is a sensitive method for PD diagnosis and severity evaluation. MK in the SN is a potential biomarker for imaging studies of early PD that can be widely used in clinic.

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.

scholarly journals Non-invasive diagnostic tool for Parkinson’s disease by sebum RNA profile with machine learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuya Uehara ◽  
Shin-Ichi Ueno ◽  
Haruka Amano-Takeshige ◽  
Shuji Suzuki ◽  
Yoko Imamichi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Alpha Synuclein ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Non Invasive

AbstractParkinson's disease (PD) is a progressive neurodegenerative disease presenting with motor and non-motor symptoms, including skin disorders (seborrheic dermatitis, bullous pemphigoid, and rosacea), skin pathological changes (decreased nerve endings and alpha-synuclein deposition), and metabolic changes of sebum. Recently, a transcriptome method using RNA in skin surface lipids (SSL-RNAs) which can be obtained non-invasively with an oil-blotting film was reported as a novel analytic method of sebum. Here we report transcriptome analyses using SSL-RNAs and the potential of these expression profiles with machine learning as diagnostic biomarkers for PD in double cohorts (PD [n = 15, 50], controls [n = 15, 50]). Differential expression analysis between the patients with PD and healthy controls identified more than 100 differentially expressed genes in the two cohorts. In each cohort, several genes related to oxidative phosphorylation were upregulated, and gene ontology analysis using differentially expressed genes revealed functional processes associated with PD. Furthermore, machine learning using the expression information obtained from the SSL-RNAs was able to efficiently discriminate patients with PD from healthy controls, with an area under the receiver operating characteristic curve of 0.806. This non-invasive gene expression profile of SSL-RNAs may contribute to early PD diagnosis based on the neurodegeneration background.

scholarly journals Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sagnik Sen ◽  
Ashmita Dey ◽  
Ujjwal Maulik
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sequence Space ◽  
Late Onset ◽  
Structural Information ◽  
Semantic Networks ◽  
Alpha Synuclein ◽  
Functional Adaptation ◽  
Missense Mutations ◽  
Structural Variability

AbstractParkinson’s disease is a common neurodegenerative disease. The differential expression of alpha-synuclein within Lewy Bodies leads to this disease. Some missense mutations of alpha-synuclein may resultant in functional aberrations. In this study, our objective is to verify the functional adaptation due to early and late-onset mutation which can trigger or control the rate of alpha-synuclein aggregation. In this regard, we have proposed a computational model to study the difference and similarities among the Wild type alpha-synuclein and mutants i.e., A30P, A53T, G51D, E46K, and H50Q. Evolutionary sequence space analysis is also performed in this experiment. Subsequently, a comparative study has been performed between structural information and sequence space outcomes. The study shows the structural variability among the selected subtypes. This information assists inter pathway modeling due to mutational aberrations. Based on the structural variability, we have identified the protein–protein interaction partners for each protein that helps to increase the robustness of the inter-pathway connectivity. Finally, few pathways have been identified from 12 semantic networks based on their association with mitochondrial dysfunction and dopaminergic pathways.

scholarly journals Neurocognitive Correlates of Apathy and Anxiety in Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yelena Bogdanova ◽  
Alice Cronin-Golomb
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychological Tests ◽  
Rating Scales ◽  
Disease Duration ◽  
Differential Association ◽  
Motor Symptoms ◽  
Healthy Controls ◽  
Nonmotor Symptoms ◽  
Neurocognitive Profiles

Parkinson's disease (PD) is associated with various nonmotor symptoms including neuropsychiatric and cognitive dysfunction. We examined the relation between apathy, anxiety, side of onset of motor symptoms, and cognition in PD. We hypothesized that PD patients would show different neuropsychiatric and neurocognitive profiles depending on the side of onset. 22 nondemented PD patients (11 right-side onset (RPD) with predominant left-hemisphere pathology, and 11 LPD) and 22 matched healthy controls (NC) were administered rating scales assessing apathy and anxiety, and a series of neuropsychological tests. PD patients showed a higher anxiety level than NC. There was a significant association between apathy, anxiety, and disease duration. In LPD, apathy but not anxiety was associated with performance on nonverbally mediated executive function and visuospatial measures, whereas, in RPD, anxiety but not apathy correlated with performance on verbally mediated tasks. Our findings demonstrated a differential association of apathy and anxiety to cognition in PD.

scholarly journals Alpha-Synuclein in the Gastrointestinal Tract as a Potential Biomarker for Early Detection of Parkinson’s Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8666
Author(s):  
Dominika Fricova ◽  
Jana Harsanyiova ◽  
Alzbeta Kralova Trancikova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Clinical Symptoms ◽  
Neuronal Degeneration ◽  
Alpha Synuclein ◽  
Diagnostic Methods ◽  
Alternative Methods ◽  
Peripheral Tissues ◽  
Potential Biomarker

The primary pathogenesis associated with Parkinson’s disease (PD) occurs in peripheral tissues several years before the onset of typical motor symptoms. Early and reliable diagnosis of PD could provide new treatment options for PD patients and improve their quality of life. At present, however, diagnosis relies mainly on clinical symptoms, and definitive diagnosis is still based on postmortem pathological confirmation of dopaminergic neuronal degeneration. In addition, the similarity of the clinical, cognitive, and neuropathological features of PD with other neurodegenerative diseases calls for new biomarkers, suitable for differential diagnosis. Alpha-synuclein (α-Syn) is a potential PD biomarker, due to its close connection with the pathogenesis of the disease. Here we summarize the currently available information on the possible use of α-Syn as a biomarker of early stages of PD in gastrointestinal (GI) tissues, highlight its potential to distinguish PD and other neurodegenerative diseases, and suggest alternative methods (primarily developed for other tissue analysis) that could improve α-Syn detection procedures or diagnostic methods in general.

scholarly journals Eosinophil-Derived Neurotoxin Is Elevated in Patients with Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Guan-Ting Liu ◽  
Chi-Shin Hwang ◽  
Chia-Hung Hsieh ◽  
Chih-Hao Lu ◽  
Sunny Li-Yun Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
High Mobility ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Lateral Sclerosis

Background and Objectives. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS.Materials and Methods. We examined 44 patients with ALS, 41 patients with Alzheimer’s disease, 41 patients with Parkinson’s disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay.Results. EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P<0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson’s disease and Alzheimer’s disease and healthy controls were similar.Conclusion. A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.

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