α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy

AbstractThe diagnosis of Parkinson’s disease (PD) and atypical parkinsonian syndromes is difficult due to the lack of reliable, easily accessible biomarkers. Multiple system atrophy (MSA) is a synucleinopathy whose symptoms often overlap with PD. Exosomes isolated from blood by immunoprecipitation using CNS markers provide a window into the brain’s biochemistry and may assist in distinguishing between PD and MSA. Thus, we asked whether α-synuclein (α-syn) in such exosomes could distinguish among healthy individuals, patients with PD, and patients with MSA. We isolated exosomes from the serum or plasma of these three groups by immunoprecipitation using neuronal and oligodendroglial markers in two independent cohorts and measured α-syn in these exosomes using an electrochemiluminescence ELISA. In both cohorts, α-syn concentrations were significantly lower in the control group and significantly higher in the MSA group compared to the PD group. The ratio between α-syn concentrations in putative oligodendroglial exosomes compared to putative neuronal exosomes was a particularly sensitive biomarker for distinguishing between PD and MSA. Combining this ratio with the α-syn concentration itself and the total exosome concentration, a multinomial logistic model trained on the discovery cohort separated PD from MSA with an AUC = 0.902, corresponding to 89.8% sensitivity and 86.0% specificity when applied to the independent validation cohort. The data demonstrate that a minimally invasive blood test measuring α-syn in blood exosomes immunoprecipitated using CNS markers can distinguish between patients with PD and patients with MSA with high sensitivity and specificity. Future optimization and validation of the data by other groups would allow this strategy to become a viable diagnostic test for synucleinopathies.

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Early effect of thalamotomy on cognitive function in patients with Parkinson’s disease

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2018-0005 ◽

2018 ◽

Vol 14 (1) ◽

Author(s):

Edward J. Gorzelańczyk ◽

Dorota Ackermann-Szulgit ◽

Marek Kunc ◽

Marek Harat ◽

Piotr Walecki

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Function ◽

Verbal Memory ◽

Spatial Working Memory ◽

Verbal Learning ◽

Control Group ◽

Healthy Individuals ◽

Early Effect ◽

Visual Spatial

Abstract Thalamotomy is a neurosurgical procedure used in the treatment of advanced Parkinson’s disease (PD). The aim of our research is to evaluate the early impact of a lesion in the ventrointermedial nucleus (VIM) of the thalamus on cognitive and motor function in people with PD. Sixty patients who qualified for right- or left-sided VIM thalamotomy were involved in the study. The cognitive and motor functions of each patient were assessed both prior to and following the surgical procedure. Twenty-nine PD patients without ablative treatment were qualified for the comparison group, and 57 neurologically healthy individuals were assigned to the control group. The following tests were carried out: Mini Mental State Examination, Benton Visual Retention Test, Stroop Color and Word Test, Trail Making Test A&B, and Rey Auditory Verbal Learning Test. Statistically significant differences were found in reaction time, visual-spatial working memory, auditory-verbal memory, and overall level of cognitive function when comparing the results of tests carried out before and after thalamotomy and when comparing patients who had undergone surgery with untreated or healthy individuals. In patients with right-sided and left-sided thalamotomy differences were also found in the mean number of perseverative errors and recalled words.

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Impact of Manual Coordination on Usability of Clothing Fasteners in People With Parkinson’s Disease

Ergonomics in Design The Quarterly of Human Factors Applications ◽

10.1177/10648046211005573 ◽

2021 ◽

pp. 106480462110055

Author(s):

Leticia Nardoni Marteli ◽

Fabio Augusto Barbieri ◽

Gabriel Gerizani ◽

Érica Pereira das Neves ◽

Luis Carlos Paschoarelli

Keyword(s):

Older Adults ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Skills ◽

Daily Life ◽

Control Group ◽

Healthy Individuals ◽

Group Coordination

People with Parkinson’s disease (PD) manipulate clothing as part of their daily life. To understand how deteriorating motor skills affect the performance of dressing/undressing activities, this study investigated performance in handling clothing fastening. Participants were distributed into two groups: older adults with PD and neurologically matched healthy individuals (control group). Coordination and usability were evaluated. The PD group demonstrated worse performance than the control group in usability for types of buttons, and this was affected more intensely by small compared with large fasteners. This study demonstrated the need for increased awareness by clothing companies to develop products that can promote independence.

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Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.648531 ◽

2021 ◽

Vol 13 ◽

Author(s):

Wen-biao Xian ◽

Xin-chong Shi ◽

Gan-hua Luo ◽

Chang Yi ◽

Xiang-song Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Positron Emission Tomography ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Statistical Parametric Mapping ◽

Emission Tomography ◽

Control Group ◽

Healthy Controls ◽

Positron Emission ◽

Segmentation Analysis

It is difficult to differentiate between Parkinson's disease and multiple system atrophy parkinsonian subtype (MSA-P) because of the overlap of their signs and symptoms. Enormous efforts have been made to develop positron emission tomography (PET) imaging to differentiate these diseases. This study aimed to investigate the co-registration analysis of 18F-fluorodopa and 18F-flurodeoxyglucose PET images to visualize the difference between Parkinson's disease and MSA-P. We enrolled 29 Parkinson's disease patients, 28 MSA-P patients, and 10 healthy controls, who underwent both 18F-fluorodopa and 18F-flurodeoxyglucose PET scans. Patients with Parkinson's disease and MSA-P exhibited reduced bilateral striatal 18F-fluorodopa uptake (p < 0.05, vs. healthy controls). Both regional specific uptake ratio analysis and statistical parametric mapping analysis of 18F-flurodeoxyglucose PET revealed hypometabolism in the bilateral putamen of MSA-P patients and hypermetabolism in the bilateral putamen of Parkinson's disease patients. There was a significant positive correlation between 18F-flurodeoxyglucose uptake and 18F-fluorodopa uptake in the contralateral posterior putamen of MSA-P patients (rs = 0.558, p = 0.002). Both 18F-flurodeoxyglucose and 18F-fluorodopa PET images showed that the striatum was rabbit-shaped in the healthy control group segmentation analysis. A defective rabbit-shaped striatum was observed in the 18F-fluorodopa PET image of patients with Parkinson's disease and MSA-P. In the segmentation analysis of 18F-flurodeoxyglucose PET image, an intact rabbit-shaped striatum was observed in Parkinson's disease patients, whereas a defective rabbit-shaped striatum was observed in MSA-P patients. These findings suggest that there were significant differences in the co-registration analysis of 18F-flurodeoxyglucose and 18F-fluorodopa PET images, which could be used in the individual analysis to differentiate Parkinson's disease from MSA-P.

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Residual signal auto-correlation to evaluate speech in Parkinson’s disease patients

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2006000600004 ◽

2006 ◽

Vol 64 (4) ◽

pp. 912-915 ◽

Cited By ~ 6

Author(s):

José Carlos Pereira ◽

Arthur Oscar Schelp ◽

Arlindo Neto Montagnoli ◽

Ana Rita Gatto ◽

André Augusto Spadotto ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Statistical Difference ◽

Control Group ◽

Healthy Individuals ◽

Age And Gender ◽

Residual Signal ◽

Auto Correlation ◽

Significant Difference ◽

And Gender

OBJECTIVE: To evaluate the maximum residual signal auto-correlation also known as pitch amplitude (PA) values in patients with Parkinson’s disease (PD) patients. METHOD: The signals of 21 Parkinson’s patients were compared with 15 healthy individuals, divided according age and gender. RESULTS: Statistical difference was seen between groups for PA, 0.39 for controls and 0.25 for PD. Normal value threshold was set as 0.3; (p<0.001). In the Parkinson’s group 80.77%, and in the control group only 12.28%, had a PA<0.3 demonstrating an association between these variables. The dispersion diagram for age and PA for PD individuals showed p=0.01 and r=0.54. There was no significant difference in relation to gender and PA between groups. CONCLUSION: The significant differences in pitch’s amplitude between PD patients and healthy individuals demonstrate the methods specificity. The results showed the need of prospective controlled studies to improve the use and indications of residual signal auto-correlation to evaluate speech in PD patients.

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Characterization of gait variability in multiple system atrophy and Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-020-10355-y ◽

2020 ◽

Author(s):

Victoria Sidoroff ◽

Cecilia Raccagni ◽

Christine Kaindlstorfer ◽

Sabine Eschlboeck ◽

Alessandra Fanciulli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Stride Length ◽

Gait Variability ◽

Postural Instability ◽

Gait Velocity ◽

Control Group ◽

Stride Time ◽

Stance Time

Abstract Background Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. Objectives We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson’s disease, and a control group of older adults. Methods Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson’s disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. Results Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson’s patients did not. Compared with Parkinson’s disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. Conclusion This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson’s disease patients and controls.

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Cerebrospinal Fluid Levels of Chromogranin A in Parkinson’s Disease and Multiple System Atrophy

Brain Sciences ◽

10.3390/brainsci11020141 ◽

2021 ◽

Vol 11 (2) ◽

pp. 141

Author(s):

Michaela Kaiserova ◽

Monika Chudackova ◽

Katerina Mensikova ◽

Miroslav Vastik ◽

Sandra Kurcova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Multiple System Atrophy ◽

Chromogranin A ◽

Disease Duration ◽

Statistical Significance ◽

Control Group ◽

Dose Equivalent ◽

Levodopa Dose

Background: Chromogranin A (CgA) and other peptides from the chromogranin–secretogranin family have been recently studied as potential biomarkers of various neurodegenerative diseases, including Parkinson’s disease (PD). Methods: We measured CgA in the cerebrospinal fluid (CSF) of 119 PD patients, 18 multiple system atrophy (MSA) patients, and 31 age-matched controls. We also correlated the values with disease duration and levodopa dose equivalent. Results: In the PD patients, CSF CgA tended to be lower than the control group (median 124.5 vs. 185.2 µg/L; p = 0.057); however, the results did not reach statistical significance. CSF CgA levels in MSA were significantly lower compared to the control group (median 104.4 vs. 185.2; p = 0.014). There was no significant difference in CSF CgA between PD and MSA patients (p = 0.372). There was no association between CSF CgA and disease duration or levodopa dose equivalent in PD or in MSA. Conclusions: We observed a tendency toward lower CSF CgA levels in both PD and MSA compared to the control group; however, the difference reached statistical significance only in MSA. Based on these results, CgA may have potential as a biomarker in PD and MSA, but further studies on larger numbers of patients are needed to draw conclusions.

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Serum Homocysteine Level in Parkinson’s Disease and Its Association with Duration, Cardinal Manifestation, and Severity of Disease

Parkinson s Disease ◽

10.1155/2018/5813084 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Payam Saadat ◽

Alijan Ahmadi Ahangar ◽

Seyed Ehsan Samaei ◽

Alireza Firozjaie ◽

Fatemeh Abbaspour ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Homocysteine Level ◽

Financial Burden ◽

Multivariate Logistic Regression Analysis ◽

High Serum ◽

Control Group ◽

Healthy Individuals ◽

Mobility Impairment ◽

Serum Homocysteine

Background and Purpose. Due to the high prevalence of Parkinson’s disease (PD) in the elderly, a large financial burden is imposed on the families and health systems of countries in addition to the problems related to the mobility impairment caused by the disease for the patients. Studies on controversial issues in this disease are taken into consideration, and one of these cases is the role of serum homocysteine level in Parkinson’s patients. In this study, the serum level of homocysteine and its association with various variables in relation to this disease was compared with healthy individuals. Materials and Methods. In this study, 100 patients with PD and 100 healthy individuals as control group were investigated. Serum homocysteine level and demographic and clinical data were included in the checklist. Data were analyzed by SPSS version 23. In all tests, the significance level was below 0.05. Results. The mean level of serum homocysteine in case and control groups was 14.93 ± 8.30 and 11.52 ± 2.86 µmol/L, respectively (95% CI: 1.68; 5.14, P<0.001). In total patients, 85 had normal serum homocysteine level, while 15 had high serum homocysteine level. In controls, the homocysteine level was 98 and 2, respectively (P=0.002). In multivariate logistic regression analysis, serum homocysteine level higher than 20 µmol/L was accompanied by 8.64-fold in Parkinson’s disease involvement (95% CI: 1.92; 38.90, P=0.005). Conclusion. Increasing serum homocysteine level elevates the rate to having PD. Serum homocysteine levels did not have any relationship with the duration of the disease, type of cardinal manifestation, and the severity of Parkinson’s disease.

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