Circulating Inflammatory miRNAs Associated with Parkinson’s Disease Pathophysiology

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, being largely characterized by motor features. MicroRNAs (miRNAs) are small non-coding RNAs, whose deregulation has been associated with neurodegeneration in PD. In this study, miRNAs targeting cell death and/or inflammation pathways were selected and their expression compared in the serum of PD patients and healthy controls. We used two independent cohorts (discovery and validation) of 20 idiopathic PD patients (iPD) and 20 healthy controls each. We also analyzed an additional group of 45 patients with a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2-PD). miRNA expression was determined using Taqman qRT-PCR and their performance to discriminate between groups was assessed by receiver operating characteristic (ROC) curve analysis. We found miR-146a, miR-335-3p, and miR-335-5p downregulated in iPD and LRRK2-PD patients versus controls in both cohorts. In addition, miR-155 was upregulated in LRRK2-PD compared to iPD patients showing an appropriate value of area under the ROC curve (AUC 0.80) to discriminate between the two groups. In conclusion, our study identified a panel of inflammatory related miRNAs differentially expressed between PD patients and healthy controls that highlight key pathophysiological processes and may contribute to improve disease diagnosis.

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Cell Ratio Differences in Peripheral Blood between Early- and Late-Onset Parkinson’s Disease: A Case-Control Study

BioMed Research International ◽

10.1155/2019/2072635 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Sen Jiang ◽

Yuling Wang ◽

Hua Gao ◽

Qin Luo ◽

Dan Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Roc Curve ◽

Late Onset ◽

Diagnostic Value ◽

Curve Analysis ◽

Onset Age ◽

Immune Disorders ◽

Roc Curve Analysis ◽

Cell Ratio

Objectives. To explore the differences of immune disorders in peripheral blood between patients with early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD). Methods. We retrospectively reviewed medical records of Parkinson’s disease (PD) patients and healthy controls between June 2002 and July 2017. At last, we included 117 PD patients who were divided into EOPD and LOPD according to whether onset age of PD was after 50 and 99 controls divided into E-Control (match for EOPD) and L-Control (match for LOPD) according to whether their age was after 53 which was onset age plus median of disease duration. We compared the ratios of cells between multiple groups and performed the multinominal logistic regression analysis to explore the relationship between ratios and subtypes of PD. We also carried out the receiver operating characteristic (ROC) curve analysis to estimate the diagnostic value of the variable. Results. Lymphocyte-red blood cell ratio (LRR) was lower in LOPD compared with that in EOPD or L-Control. LRR was also negatively associated with LOPD (OR: 0.623; 95% CI: 0.397–0.980; P=0.040). The ROC curve analysis showed the optimal cutoff value of 4.53 (×10−4) of LRR for discrimination of LOPD versus L-Control (sensitivity: 0.596, specificity: 0.764). The area under curve (AUC) was 0.721. As for LOPD versus EOPD, the optimal threshold of LRR was 4.10 (×10−4) (sensitivity: 0.516, specificity: 0.745). AUC was 0.641. Conclusions. Peripheral immune disorders might play an important part in the pathological progression of LOPD. Also, LRR has potential diagnostic value.

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Parkinson’s Disease Is Associated With Dysregulation of Circulatory Levels of lncRNAs

Frontiers in Immunology ◽

10.3389/fimmu.2021.763323 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kasra Honarmand Tamizkar ◽

Pooneh Gorji ◽

Mahdi Gholipour ◽

Bashdar Mahmud Hussen ◽

Mehrdokht Mazdeh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Stage ◽

P Value ◽

Roc Curve Analysis ◽

Expression Ratio ◽

Male And Female ◽

Female Patients ◽

Male Patients ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs) have been recently reported to be involved in the pathoetiology of Parkinson’s disease (PD). Circulatory levels of lncRNAs might be used as markers for PD. In the present work, we measured expression levels of HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs in the circulation of patients with PD versus healthy controls. Expression of HULC was lower in total patients compared with total controls (Expression ratio (ER)=0.19, adjusted P value<0.0001) as well as in female patients compared with female controls (ER=0.071, adjusted P value=0.0004). Expression of PVT1 was lower in total patients compared with total controls (ER=0.55, adjusted P value=0.0124). Expression of DSCAM-AS1 was higher in total patients compared with total controls (ER=5.67, P value=0.0029) and in male patients compared with male controls (ER=9.526, adjusted P value=0.0024). Expression of SPRY4-IT was higher in total patients compared with total controls (ER=2.64, adjusted P value<0.02) and in male patients compared with male controls (ER=3.43, P value<0.03). Expression of LINC-ROR was higher in total patients compared with total controls (ER=10.36, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=4.57, adjusted P value=0.03 and ER=23.47, adjusted P value=0.0019, respectively). Finally, expression of MEG3 was higher in total patients compared with total controls (ER=13.94, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=8.60, adjusted P value<0.004 and ER=22.58, adjusted P value<0.0085, respectively). ROC curve analysis revealed that MEG3 and LINC-ROR have diagnostic power of 0.77 and 0.73, respectively. Other lncRNAs had AUC values less than 0.7. Expression of none of lncRNAs was correlated with age of patients, disease duration, disease stage, MMSE or UPDRS. The current study provides further evidence for dysregulation of lncRNAs in the circulation of PD patients.

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Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson’s disease

Translational Neurodegeneration ◽

10.1186/s40035-021-00249-y ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Shulei He ◽

Lu Huang ◽

Ci Shao ◽

Tiejian Nie ◽

Li Xia ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Extracellular Vesicles ◽

Unmet Need ◽

Functional Enrichment ◽

Differentially Expressed ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Qrt Pcr

Abstract Background Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. Methods A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. Results WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. Conclusions The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.

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Expression Analysis of NF-κB-Related lncRNAs in Parkinson’s Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.755246 ◽

2021 ◽

Vol 12 ◽

Author(s):

Soudeh Ghafouri-Fard ◽

Mahdi Gholipour ◽

Atefe Abak ◽

Mehrdokht Mazdeh ◽

Mohammad Taheri ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Expression Pattern ◽

Sensitivity And Specificity ◽

P Value ◽

Healthy Controls ◽

Similar Expression Pattern ◽

Non Coding Rnas ◽

Best Parameters ◽

Healthy Persons

Parkinson’s disease (PD) has been shown to affect approximately 1% of the persons aged more than 65 years. This multifactorial disorder has been associated with abnormal function of NF-κB signals. In this research, we have evaluated expressions of NF-κB-related long non-coding RNAs in the circulation of PD patients compared with healthy controls. Expression of PACER was lower in total PD patients compared with healthy persons (Ratio of mean expressions (RME)=0.32, P value<0.001). This pattern was also evident among males (RME=0.25, P value<0.001). Expression of DILC was higher in total PD patients (RME=4.07, P value<0.001), and in both sex-based subgroups (RME=3.77, P value=0.01 and RME=4.25, P value<0.001, for females and males, respectively). Similarly, CEBPA was significantly over-expressed in total PD patients (RME=14.76, P value<0.001), and in both sex-based subgroups (RME=12.42, P value<0.001 and RME=15.80, P value<0.001, for females and males, respectively). ATG5 had a similar expression pattern (RME=2.6, P value=1E-08, RME=1.73, P value=0.03 and RME=3.09, P value=1E-07, for total cases, females and males, respectively). H19 was up-regulated in total cases and male cases compared with corresponding controls (RME=2.19, P value<0.001, RME=2.68, P value=0.01, respectively). Finally, HNFA1-AS was down-regulated in all comparisons (RME=0.10, P value=2E-06, RME=0.08, P value<0.001 and RME=0.12, P value<0.001, for total cases, females and males, respectively). Among PD patients, expressions of NKILA and ADINR were robustly correlated with each other (r=0.75, P value=2.40E-10). In addition, expression levels of DICER1-AS were significantly correlated with those of ADINR, PACER and H19 in these patients (r=0.73, P value=1.76E-9; r=0.72, P value=5.15E-09 and r=0.72, P value=3.09E-09, respectively). Correlation analyses among healthy controls revealed robust correlations between CHAST and CEBPA (r=0.84, P value=3.09E-09), NKILA and ADINR (r=0.80, P value=4.24E-12) as well as between DILC and CHAST (r=0.76, P value=1.70E-10). CEBPA had the best parameters among all assessed genes (AUC=0.96, Sensitivity=0.90 and specificity=0.97). DILC and ATG5 were the most appropriate markers after CEBPA with AUC values of 0.82 and 0.80, respectively. Most notably, combination of all genes improved AUC, sensitivity and specificity parameters to 1, 0.97 and 0.99, respectively. Cumulatively, the current study provides evidence for participation of NF-κB-related lncRNAs in the pathoetiology of PD.

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Parkinson’s disease diagnosis using convolutional neural networks and figure-copying tasks

Neural Computing and Applications ◽

10.1007/s00521-021-06469-7 ◽

2021 ◽

Author(s):

Mohamad Alissa ◽

Michael A. Lones ◽

Jeremy Cosgrove ◽

Jane E. Alty ◽

Stuart Jamieson ◽

...

Keyword(s):

Neural Network ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Network Architecture ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Disease Diagnosis ◽

Healthy Controls ◽

Abnormal Movements ◽

Drawing Tasks

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder that causes abnormal movements and an array of other symptoms. An accurate PD diagnosis can be a challenging task as the signs and symptoms, particularly at an early stage, can be similar to other medical conditions or the physiological changes of normal ageing. This work aims to contribute to the PD diagnosis process by using a convolutional neural network, a type of deep neural network architecture, to differentiate between healthy controls and PD patients. Our approach focuses on discovering deviations in patient’s movements with the use of drawing tasks. In addition, this work explores which of two drawing tasks, wire cube or spiral pentagon, are more effective in the discrimination process. With $$93.5\%$$ 93.5 % accuracy, our convolutional classifier, trained with images of the pentagon drawing task and augmentation techniques, can be used as an objective method to discriminate PD from healthy controls. Our compact model has the potential to be developed into an offline real-time automated single-task diagnostic tool, which can be easily deployed within a clinical setting.

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Pareidolia in Parkinson’s Disease and Multiple System Atrophy

Parkinson s Disease ◽

10.1155/2021/2704755 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Kentaro Kurumada ◽

Atsuhiko Sugiyama ◽

Shigeki Hirano ◽

Tatsuya Yamamoto ◽

Yoshitaka Yamanaka ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Sensitivity And Specificity ◽

Trait Anxiety ◽

Roc Curve ◽

Visual Hallucinations ◽

State Trait Anxiety Inventory ◽

Roc Curve Analysis ◽

Specific Test

Pareidolia is a visual illusion of meaningful objects that arise from ambiguous forms embedded in visual scenes. Previous studies showed that pareidolias are frequently observed in patients with Parkinson’s disease (PD) as well as dementia with Lewy bodies. However, whether pareidolias are useful for differentiating PD from other neurodegenerative parkinsonism disorders including multiple system atrophy (MSA) is unclear. The noise pareidolia test (NPT) was performed in 40 and 48 patients with PD and MSA, respectively. A receiver operating characteristic (ROC) curve analysis was used to evaluate sensitivity and specificity. Results of neuropsychological tests were also compared between patients with PD with and without pareidolias. Visual hallucinations were present in none of the subjects. Pareidolic response in the NPT was observed in 47.5% and 18.8% of patients with PD and MSA, respectively. The number of pareidolic responses in patients with PD was significantly larger compared with patients with MSA ( P = 0.001 ). ROC curve analyses showed the sensitivity and specificity at 33% and 98%, respectively. Among patients with PD, those with pareidolias demonstrated higher State-Trait Anxiety Inventory-state ( P = 0.044 ) and State-Trait Anxiety Inventory-trait ( P = 0.044 ) than those without pareidolias. Pareidolias can be found in patients with PD without visual hallucinations, and the pareidolia test may be a highly specific test for differentiating PD from MSA. Thus, anxiety may be associated with pareidolias in patients with PD.

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A Japanese prospective multicenter study of urinary oxysterols in biliary atresia

Scientific Reports ◽

10.1038/s41598-021-84445-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ken-ichiro Konishi ◽

Tatsuki Mizuochi ◽

Hajime Takei ◽

Ryosuke Yasuda ◽

Hirotaka Sakaguchi ◽

...

Keyword(s):

Biliary Atresia ◽

Multicenter Study ◽

Roc Curve ◽

Operating Characteristic ◽

Curve Analysis ◽

Tandem Mass ◽

Healthy Controls ◽

Japanese Children ◽

Roc Curve Analysis ◽

Prospective Multicenter Study

AbstractDiagnosis of biliary atresia (BA) can involve uncertainties. In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6 months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4β-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68 days; range 26–170) and 10 non-BA cholestatic controls (59; 14–162), as well as 10 HC (57; 25–120). Total urinary oxysterols were significantly greater in BA (median, 153.0 μmol/mol creatinine; range 24.1–486.7; P < 0.001) and non-BA (36.2; 5.8–411.3; P < 0.05) than in HC (2.7; 0.8–7.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42–11.09; P < 0.01) was significantly greater than in non-BA (0.71; 0–5.62). In receiver operating characteristic (ROC) curve analysis for distinguishing BA from non-BA, the area under the ROC curve for urinary 27-hydroxycholesterol was 0.83. In conclusion, this first report of urinary oxysterol analysis in patients with BA indicated that 27-hydroxycholesterol may be a useful marker for distinguishing BA from other causes of neonatal cholestasis.

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