A systematic review of biofluid phosphorylated α-synuclein in Parkinson's disease.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease, and biomarkers are needed to enhance earlier detection and monitoring. Alpha-synuclein, phosphorylated at serine 129 (pS129-α-syn), is the predominant form of α-syn found in Lewy bodies implicating an involvement in disease pathology. This review aims to systematically evaluate the evidence for pS129-α-syn detection in human biofluid samples of PD utilizing ELISA-based protein detection methods.

Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons.

Purpose: The purpose of this study was to examine possible involvement of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1/Flt-1 in pigment epithelium-derived factor (PEDF)-promoted survival of retinal neurons.

Methods: Survival of growth factor-deprived retinal ganglion cells (RGCs) and R28 cells and activation of ERK-1/-2 MAP kinases were assessed in the presence of PEDF, placental growth factor (PlGF), and VEGF using cell cultures, viability assays and quantitation of ERK-1/-2 phosphorylation. VEGFR-1/Flt-1 expression was determined using quantitative PCR (qPCR) and Western blotting.

Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson's Disease.

Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson's disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years.

Cognitive Profile in Parkinson's Disease Dementia Patients with Low versus Normal Cerebrospinal Fluid Amyloid Beta.

Introduction: In patients with Parkinson's disease (PD), low cerebrospinal fluid (CSF) amyloid beta 1-42 (Ab42) at baseline is the most consistent CSF biomarker as a risk factor for developing dementia. Low CSF Ab42 is, however, a typical hallmark of Alzheimer's disease (AD). Hence, low CSF Ab42 in patients with PD may indicate presence of comorbid AD pathology and may predict a more AD-like cognitive profile when they develop dementia.

Identification of diagnostic and prognostic biomarkers of PD using a multiplex proteomics approach.

Given the complexity of Parkinson's disease (PD), achieving acceptable diagnostic and prognostic accuracy will require the support of a panel of diverse biomarkers. We used Proximity extension assays to measure a panel of 92 proteins in CSF of 120 newly diagnosed PD patients and 45 control subjects without neurological disease. From 75 proteins detectable in the CSF of >90% of the subjects, regularized regression analysis identified four proteins (β-NGF, CD38, tau and NCAN) as downregulated in newly diagnosed PD patients (age at diagnosis 67.

Seed Amplification Assay as a Diagnostic Tool in Newly-Diagnosed Parkinson's Disease.

Seed amplification assays (SAA) are the first credible molecular assay for Parkinson's disease (PD). However, the value of SAA to support the clinicians' initial diagnosis of PD is not clear. In our study, we analyzed cerebrospinal fluid samples from 121 PD patients recruited through population screening methods and taken within a median delay of 38 days from diagnosis and 51 normal controls without neurodegenerative disease.

Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders.

Background And Objectives: Neuroinflammation contributes to Parkinson disease (PD) pathology, and inflammatory biomarkers may aid in PD diagnosis. Proximity extension assay (PEA) technology is a promising method for multiplex analysis of inflammatory markers. Neuroinflammation also plays a role in related neurodegenerative diseases, such as dementia with Lewy bodies (DLB) and Alzheimer disease (AD).

Association of CSF Glucocerebrosidase Activity With the Risk of Incident Dementia in Patients With Parkinson Disease.

Background And Objectives: Variations in the glucocerebrosidase gene () are common risk factors for Parkinson disease (PD) and dementia in PD (PDD) and cause a reduction in the activity of the lysosomal enzyme glucocerebrosidase (GCase). It is anticipated that GCase dysfunction might contribute to a more malignant disease course and predict cognitive impairment in PD, although evidence is lacking. We aimed to discover whether CSF GCase activity is altered in newly diagnosed patients with PD and associated with future development of dementia.

Practices and Attitudes of Bavarian Stakeholders Regarding the Secondary Use of Health Data for Research Purposes During the COVID-19 Pandemic: Qualitative Interview Study.

Background: The COVID-19 pandemic is a threat to global health and requires collaborative health research efforts across organizations and countries to address it. Although routinely collected digital health data are a valuable source of information for researchers, benefiting from these data requires accessing and sharing the data. Health care organizations focusing on individual risk minimization threaten to undermine COVID-19 research efforts, and it has been argued that there is an ethical obligation to use the European Union's General Data Protection Regulation (GDPR) scientific research exemption during the COVID-19 pandemic to support collaborative health research.

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson's disease.

There is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson's disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression.

Association of Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients.

To evaluate the impact of polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD. Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination.

Validation and assessment of preanalytical factors of a fluorometric in vitro assay for glucocerebrosidase activity in human cerebrospinal fluid.

Lysosomal dysfunction is an emerging feature in the pathology of Parkinson's disease and Dementia with Lewy bodies. Mutations in the GBA gene, encoding the enzyme Glucocerebrosidase (GCase), have been identified as a genetic risk factor for these synucleinopathies. As a result, there has been a growing interest in the involvement of GCase in these diseases.

Next-Generation RNA-Sequencing of Serum Small Extracellular Vesicles Discovers Potential Diagnostic Biomarkers for Dementia With Lewy Bodies.

Objective: There is an urgent clinical need for identifying blood-based diagnostic biomarkers for Dementia with Lewy Bodies (DLB). Transcriptomic studies have reported unique RNA changes in postmortem DLB brains. Small extracellular vesicles (SEV) that transport RNA between brain and peripheral circulation enable identifying molecular changes in living human brain.

Podcasts as a teaching tool in orthopaedic surgery : Is it beneficial or more an exemption card from attending lectures?

Objective: The aim of this study was to evaluate the influence of the introduction of online podcasts as part of the main lecture series in orthopaedics on the number of lecture attendees, the examination results and the assessment of teaching by the students. Additionally, we evaluated the use of other media for examination preparation.

Methodology: At the beginning and end of the lecture series questionnaires were handed out to the students to evaluate their attitudes towards attending lectures, the use of video podcasts and examination preparation.

Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia.

Introduction: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia.

Objective: The objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms.

The role of ADGRE5/CD97 in human retinal pigment epithelial cell growth and survival.

Cell surface molecules of retinal pigment epithelial (RPE) cells participate in the pathogenesis of retinal diseases. In an attempt to identify cell surface proteins that play a role in RPE cell-cell interactions, we have considered studying the expression, regulation, and signaling of ADGRE5/CD97, an adhesion G protein-coupled receptor family member, based on its known adhesive function in other cell types such as leukocytes. We showed that RPE cells express three isoforms of CD97 and identified inflammation-related cytokines as important mediators regulating CD97 expression.

Combinatory microRNA serum signatures as classifiers of Parkinson's disease.

Introduction: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts.

Methods: 370 PD (drug naïve) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMeå (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR.

Evolution of cerebrospinal fluid total α-synuclein in Parkinson's disease.

Introduction: Cerebrospinal fluid (CSF) total α-synuclein is considered a potential biomarker for Parkinson's disease (PD), but little is known about the evolution of this marker during the course of the disease. Our objective was to investigate whether CSF total α-synuclein concentrations change over time and are associated with motor and cognitive function in PD.

Methods: CSF total α-synuclein concentrations were quantified in 56 longitudinally followed PD patients, 27 of whom provided CSF repeatedly 2 and/or 4 years later.

Validation of a new assay for α-synuclein detection in cerebrospinal fluid.

Background: Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein.

Patient reported outcome measurements in the diagnosis of incisional hernia: PROMIS questionnaire, a pilot study.

Background: Incisional hernia (IH) is the most frequent complication after abdominal surgery. Long-term follow-up is crucial. Patient-reported outcome measurements (PROMs) are able to monitor patients' disease progression after treatment.

Association of a BACE1 Gene Polymorphism with Parkinson's Disease in a Norwegian Population.

Background. Parkinson's disease (PD) and Alzheimer's disease (AD) share pathological features, including amyloid-beta pathology. Amyloid-beta peptide is generated by sequential proteolysis of amyloid precursor protein (APP), and genetic variations in the processing pathway genes have been found to increase the risk of AD; however, the contribution in PD is unknown.

Müller glial cells inhibit proliferation of retinal endothelial cells via TGF-β2 and Smad signaling.

Neovascularization is a sight-threatening complication of ischemic proliferative retinopathies. Transforming growth factor (TGF)-β, a cytokine with multiple functions in the retina, participates in the control of pathological angiogenesis and neovascularization. Retinal glial (Müller) cells produce TGF-β2 under physiological and post-ischemic conditions.