scholarly journals Serum neuronal exosomes predict and differentiate Parkinson’s disease from atypical parkinsonism

2020 ◽  
Vol 91 (7) ◽  
pp. 720-729 ◽  
Author(s):  
Cheng Jiang ◽  
Franziska Hopfner ◽  
Antigoni Katsikoudi ◽  
Robert Hein ◽  
Candan Catli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Disease Progression ◽  
Lewy Bodies ◽  
Training Group ◽  
Cross Sectional Study ◽  
Atypical Parkinsonism ◽  
Serum Samples ◽  
Cross Sectional

ObjectiveParkinson’s disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson’s from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson’s disease, multiple system atrophy and other proteinopathies.MethodsWe performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson’s and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.ResultsMean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson’s disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson’s disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson’s disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson’s disease progression.ConclusionsIncreased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson’s disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson’s disease from atypical parkinsonism.

scholarly journals Platelet miRNA bio-signature discriminates between dementia with Lewy bodies and Alzheimer disease

2020 ◽  
Author(s):  
Ana Gámez-Valero ◽  
Jaume Campdelacreu ◽  
Dolores Vilas ◽  
Lourdes Ispierto ◽  
Daniela Samaniego ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dementia With Lewy Bodies ◽  
Correct Diagnosis ◽  
Lewy Bodies ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Disease Biomarkers

ABSTRACTDementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a 7-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based bio-signature, which distinguishes DLB from AD.The paper explainedProblemDementia with Lewy bodies (DLB) presents pathological and clinical overlap with both Alzheimer’s (AD) and Parkinson’s disease (PD), which impairs its correct diagnosis. Although numerous papers report peripheral biomarkers for AD, well-established biomarkers for DLB distinguishing it from AD are still missing. Platelet miRNA transcriptome was analyzed in several works, but their putative role as disease biomarkers for neurological disorders has not been assessed. It would be of paramount importance to establish a blood-based bio-signature as a minimally invasive mean for DLB diagnosis, improving differentiation of DLB patients from controls and AD.ResultsOur study revealed that platelet miRNAs might be promising biomarkers for the correct diagnosis of DLB stratifying patients in comparison with overlapping disorders, especially AD, and may help to highlight possible disease-related processes. In this cross-sectional study, which includes 162 individuals (DLB, AD, PD and healthy controls), platelet-associated miRNA content was disease group-specific. Three different miRNA sets together with their predicted targeted pathways were defined.ImpactThis study suggests that platelet miRNA may serve as DLB biomarker allowing the correct diagnosis and stratification in an easily-applied manner in clinical settings, and may help to highlight possible disease-related processes.

scholarly journals A Comparison of Pain between Parkinson’s Disease and Multiple System Atrophy: A Clinical Cross-Sectional Survey

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
He-Yang You ◽  
Lei Wu ◽  
Hai-Ting Yang ◽  
Chen Yang ◽  
Xiao-Ling Ding
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Rating Scale ◽  
Depression Scale ◽  
Healthy Controls ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Disease Rating ◽  
Vas Scores

Background. Pain is frequent in Parkinson’s disease (PD) and Parkinson-plus syndrome. This study aimed to assess the prevalence, characteristics, therapy (especially the effect of dopaminergic therapy), and associated symptoms of pain in Parkinson's disease and multiple system atrophy (MSA) patients. Methods. Seventy-one PD patients, sixty-five MSA patients, and forty age-matched healthy controls were enrolled and evaluated by using the German pain questionnaire and visual analogue scale (VAS). In addition, the influence of pain in PD patients on anxiety, depression, and the quality of life was assessed with the Hospital Anxiety and Depression Scale (HADS) and Parkinson’s Disease Questionnaire (PDQ-39). Results. Compared to that of the healthy controls, the PD and MSA patients had a significantly higher presence of pain (P<0.01, P<0.01). PD patients had a higher presence of pain than MSA patients (P=0.007). No difference in VAS scores was observed between the PD and MSA patients (P=0.148). A total of 21 PD patients (42.85%) with pain and 13 MSA patients (43.33%) with pain received treatment. A total of 13 PD patients with pain and 6 MSA patients with pain had an improved pain intensity after using dopaminergic medication. The differences in the disease duration, Hoehn and Yahr stages, and scores on the Unified Parkinson’s Disease Rating Scale motor score, HAD-D, HAD-A, and PDQ-39 were significant between the PD patients with and without pain. Conclusion. PD and MSA patients are prone to pain with insufficient treatment. Pain interventions should be provided as soon as possible to improve the patient’s life.

scholarly journals White matter integrity and cognition in Parkinson's disease: a cross-sectional study

BMJ Open ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. e003976 ◽  
Author(s):  
Eirik Auning ◽  
Veslemøy Krohn Kjærvik ◽  
Per Selnes ◽  
Dag Aarsland ◽  
Astrid Haram ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
Cross Sectional Study ◽  
White Matter Integrity ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals Self-Reported Efficacy of Cannabis and Other Complementary Medicine Modalities by Parkinson’s Disease Patients in Colorado

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Taylor Andrew Finseth ◽  
Jessica Louise Hedeman ◽  
Robert Preston Brown ◽  
Kristina I. Johnson ◽  
Matthew Sean Binder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Support Groups ◽  
Legal Status ◽  
Cross Sectional Study ◽  
Recent Change ◽  
High Rate ◽  
Cross Sectional ◽  
Metro Area ◽  
Cam Use

Introduction. Complementary and alternative medicine (CAM) is frequently used by Parkinson’s disease (PD) patients. We sought to provide information on CAM use and efficacy in PD patients in the Denver metro area with particular attention to cannabis use given its recent change in legal status.Methods. Self-administered surveys on CAM use and efficacy were completed by PD patients identified in clinics and support groups across the Denver metro area between 2012 and 2013.Results. 207 patients (age69±11; 60% male) completed the survey. Responses to individual CAM therapy items showed that 85% of respondents used at least one form of CAM. The most frequently reported CAMs were vitamins (66%), prayer (59%), massage (45%), and relaxation (32%). Self-reported improvement related to the use of CAM was highest for massage, art therapy, music therapy, and cannabis. While only 4.3% of our survey responders reported use of cannabis, it ranked among the most effective CAM therapies.Conclusions. Overall, our cross-sectional study was notable for a high rate of CAM utilization amongst PD patients and high rates of self-reported efficacy across most CAM modalities. Cannabis was rarely used in our population but users reported high efficacy, mainly for nonmotor symptoms.

scholarly journals The “Gender Factor” in Wearing-Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Delia Colombo ◽  
Giovanni Abbruzzese ◽  
Angelo Antonini ◽  
Paolo Barone ◽  
Gilberto Bellia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cross Sectional Study ◽  
Motor Symptom ◽  
Cross Sectional ◽  
Post Hoc Analysis ◽  
Increased Risk ◽  
Wearing Off ◽  
Gender Factor ◽  
Post Hoc

Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena.Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO.Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%,P=0.045) and the WOQ-19 analysis (72.5% versus 64.0%,P=0.034). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men.Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect.

scholarly journals Caregiver Burden for Patients Diagnosed with Parkinson’s Disease: A Cross-sectional Study from Southern India

2020 ◽  
Author(s):  
Arun Kurupath ◽  
Praveen Arathil ◽  
Rahul Bansal
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caregiver Burden ◽  
Significant Positive Correlation ◽  
Mmse Score ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Positive Correlation ◽  
Updrs Score

Introduction: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder where the individual over time needs more and more assistance from their caregivers to carry on their life and that causes increasing burden on the caregiver. The burden for the caregiver is affecting them physically, mentally and also on a socioeconomic level. Aim: To examine the factors related to caregiver burden in caregivers of Parkinson’s patients. Materials and Methods: This was a cross-sectional study conducted in Parkinson’s clinic of a Tertiary Care Hospital of Kochi, on 100 Parkinsonism patients and their respective caregivers. Patients were assessed using the Unified PD Rating Scale (UPDRS), Hoehn and Yahr Scale (H&Y) and Mini-Mental State Examination (MMSE). Caregivers were assessed using Zerit’s Caregiver Burden inventory (CBI). Semi structured questionnaire was administered for socio-demographic details. Non parametric tests were done to examine the correlation among various variables. Results: Among the patients and caregivers, mean age was 70.65±7.30 and 67.31±8.56, respectively. Among the patient’s majority were males (n=74) while among caregivers, majority were females (n=73). Mean duration of disease was 6.79±2.68 years, mean caregiver burden score was 65.05±21.79, mean UPDRS score was 21.89±8.74 and had significant positive correlation with caregiver burden. Mean MMSE score was 17.19±4.91. The disease duration and UPDRS score had a significant positive correlation with caregiver burden score. MMSE score had significant negative correlation with caregiver burden score. Conclusion: This study concludes that a patient’s Parkinsonism related disability accounts for majority of caregiver burden. An early identification of factors contributing to stress in caregivers will help to avoid its persistency leading to a better insight in the caregiving role and thus in-patient care.

scholarly journals Structures of α-synuclein filaments from multiple system atrophy

2020 ◽  
Author(s):  
Manuel Schweighauser ◽  
Yang Shi ◽  
Airi Tarutani ◽  
Fuyuki Kametani ◽  
Alexey G. Murzin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Brain ◽  
Multiple System Atrophy ◽  
Recombinant Proteins ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Two Dimensional ◽  
Filamentous Inclusions

Synucleinopathies are human neurodegenerative diseases that include multiple system atrophy (MSA), Parkinson’s disease, Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) (1). Existing treatments are at best symptomatic. These diseases are characterised by the presence in brain cells of filamentous inclusions of α-synuclein, the formation of which is believed to cause disease (2, 3). However, the structures of α-synuclein filaments from human brain are not known. Here we show, using electron cryo-microscopy, that α-synuclein inclusions from MSA are made of two types of filaments, each of which consists of two different protofilaments. Non-proteinaceous molecules are present at the protofilament interfaces. By two-dimensional class averaging, we show that α-synuclein filaments from the brains of patients with MSA and DLB are different, suggesting that distinct conformers (or strains) characterise synucleinopathies. As was the case of tau assemblies (4–9), the structures of α-synuclein filaments extracted from the brains of individuals with MSA differ from those formed in vitro using recombinant proteins, with implications for understanding the mechanisms of aggregate propagation and neurodegeneration in human brain. These findings have diagnostic and potential therapeutic relevance, especially in view of the unmet clinical need to be able to image filamentous α-synuclein inclusions in human brain.

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