Biomarker For Parkinson's Disease Research Articles

Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes. Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/μg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/μg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

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 67.2 ± 9.4 years) compared to controls (age 65.4 ± 10.9 years). Higher tau (β −0.82 transformed MMSE points/year, 95% CI −1.37 to −0.27, P = 0.005) was also linked to faster cognitive decline over the first ten years after PD diagnosis. These findings provide insights into multiple aspects of PD pathophysiology and may serve as the foundation for identifying new biomarkers and therapeutic targets.

Neuromuscular assessment of force development, postural, and gait performance under cognitive-motor dual-tasking in healthy older adults and early Parkinson's disease patients: Study protocol for a cross-sectional Mobile Brain/Body Imaging (MoBI) study

Background: Neuromuscular dysfunction is common in older adults and more pronounced in neurodegenerative diseases. In Parkinson's disease (PD), a complex set of factors often prevents the effective performance of activities of daily living that require intact and simultaneous performance of the motor and cognitive tasks. Methods: The cross-sectional study includes a multifactorial mixed-measure design. Between-subject factor grouping the sample will be Parkinson’s Disease (early PD vs. healthy). The within-subject factors will be the task complexity (single- vs. dual-task) in each motor activity, i.e., overground walking, semi-tandem stance, and isometric knee extension, and a walking condition (wide vs. narrow lane) will be implemented for the overground walking activity only. To study dual-task (DT) effects, in each motor activity participants will be given a secondary cognitive task, i.e., a visual discrimination task for the overground walking, an attention task for the semi-tandem, and mental arithmetic for the isometric extension. Analyses of DT effects and underlying neuronal correlates will focus on both gait and cognitive performance where applicable. Based on an a priori sample size calculation, a total N = 42 older adults (55-75 years) will be recruited. Disease-specific changes such as laterality in motor unit behavior and cortical control of movement will be studied with high-density surface electromyography and electroencephalography during static and dynamic motor activities, together with whole-body kinematics. Discussion: This study will be one of the first to holistically address early PD neurophysiological and neuromuscular patterns in an ecologically valid environment under cognitive-motor DT conditions of different complexities. The outcomes of the study aim to identify the biomarker for early PD either at the electrophysiological, muscular or kinematic level or in the communication between these systems. Clinical Trial Registration: ClinicalTrials.Gov, NCT05477654. This study was approved by the Medical Ethical Committee (106/2021).

Association between regular physical activity and biomarker changes in early Parkinson's disease patients

IntroductionPhysical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid β (Aβ), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. MethodsThis retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. ResultsRegular physical activity was associated with a slower decline of DAT uptake in the caudate (β = 0.063, p = 0.011) and the putamen (β = 0.062, p = 0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. ConclusionRegular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

Effects of ozone treatment to the levels of neurodegeneration biomarkers after rotenone induced rat model of Parkinson’s disease

The study investigated the effects of ozone treatment on the neurodegeneration of stereotaxic rotenone-induced parkinson's disease (PD) model. The model was confirmed using the apomorphine rotation test. α-synuclein, amyloid-β, Tau, phosphorylated Tau, as well as tyrosine hydroxylase(+), nNOS(+), and glial cell counts were used to evaluate neurodegeneration in the substantia nigra pars compacta and ventral tegmental area. The experiment involved 48 Sprague-Dawley rats divided into four groups: dimethyl sulfoxide (DMSO), DMSO with ozone (O), DMSO/rotenone (R), and D/R/O. Ozone treatment significantly improved tissue α-synuclein level and TH+, nNOS+, and glial cell counts compared to the rotenone-only group. The study suggests that ozone treatment may have beneficial effects on PD biomarkers in the rotenone model. Further studies on ozone dosage, duration, and administration methods in humans could provide more evidence for its potential use in Parkinson's disease treatment.

Role of Telomeres and Telomerase in Parkinson's Disease-A New Theranostics?

Parkinson's disease (PD) is a complex condition that is significantly influenced by oxidative stress and inflammation. It is also suggested that telomere shortening (TS) is regulated by oxidative stress which leads to various diseases including age-related neurodegenerative diseases like PD. Thus, it is anticipated that PD would result in TS of peripheral blood mononuclear cells (PBMCs). Telomeres protect the ends of eukaryotic chromosomes preserving them against fusion and destruction. The TS is a normal process because DNA polymerase is unable to replicate the linear ends of the DNA due to end replication complications and telomerase activity in various cell types counteracts this process. PD is usually observed in the aged population and progresses over time therefore, disparities among telomere length in PBMCs of PD patients are recorded and it is still a question whether it has any useful role. Here, the likelihood of telomere attrition in PD and its implications concerning microglia activation, ageing, oxidative stress, and the significance of telomerase activators are addressed. Also, the possibility of telomeres and telomerase as a diagnostic and therapeutic biomarker in PD is discussed.

2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson's Disease.

Estrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Methoxestradiol (2-ME2), a 17β-estradiol (E2) metabolite, is known for its anticancer effects as observed both in vivo and in vitro. 2-ME2 affects all actively dividing cells, including neurons. The study aimed to determine whether 2-ME2 is a potentially cancer-protective or rather neurodegenerative agent in a specific tissue culture model as well as a clinical setup. In this study, 2-ME2 activity was determined in a Parkinson's disease (PD) in vitro model based on the neuroblastoma SH-SY5Y cell line. The obtained results suggest that 2-ME2 generates nitro-oxidative stress and controls heat shock proteins (HSP), resulting in DNA strand breakage and apoptosis. On the one hand, it may affect intensely dividing cells preventing cancer development; however, on the other hand, this kind of activity within the central nervous system may promote neurodegenerative diseases like PD. Thus, the translational value of 2-ME2's neurotoxic activity in a PD in vitro model was also investigated. LC-MS/MS technique was used to evaluate estrogens and their derivatives, namely, hydroxy and methoxyestrogens, in PD patients' blood, whereas the stopped-flow method was used to assess hydrogen peroxide (H2O2) levels. Methoxyestrogens and H2O2 levels were increased in patients' blood as compared to control subjects, but hydoxyestrogens were simultaneously decreased. From the above, we suggest that the determination of plasma levels of methoxyestrogens and H2O2 may be a novel PD biomarker. The presented research is the subject of the pending patent application "The use of hydrogen peroxide and 17β-estradiol and its metabolites as biomarkers in the diagnosis of neurodegenerative diseases," no. P.441360.

A lysosome-targeting ratiometric fluorescent probe used to detect Nitroxyl (HNO) in a Parkinson's disease model

Parkinson's disease (PD) is a neurodegenerative disease common in middle-aged and older individuals. At present, the exact cause is unknown, and the diagnosis is cumbersome, which seriously hinders the early diagnosis of patients. During the same time, during PD, there are conditions for the formation of nitroxyl (HNO). In addition, it has been shown that HNO has toxic effects on dopaminergic neurons and can lead to depletion of Glutathione (GSH), which is associated with features of PD. Therefore, HNO could be used as a potential biomarker for PD. Unfortunately, studies on changes in HNO content during PD are rarely reported. Here, we synthesized the first near-infrared ratiometric fluorescent probe HX-HNO for detecting HNO content in a PD model. The probe has excellent selectivity and sensitivity, and can detect HNO produced in various biochemical processes. Most importantly, in a PD model generated by rotenone, HX-HNO detected elevated levels of HNO. The visualization of HNO by HX-HNO provides a powerful tool for the early diagnosis of PD.

ErbB2pY -1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification.

This study aims to reveal a promising biomarker for Parkinson's disease (PD) based on research with reverse phase protein array (RPPA) technology for the first time and in vivo verification, which gains time for early intervention in PD, thus increasing the effectiveness of treatment and reducing disease morbidity. We employed RPPA technology which can assess both total and post-translationally modified proteins to identify biomarker candidates of PD in a cellular PD model. As a result, the phosphorylation (pY-1248) of the epidermal growth factor receptor (EGFR) ErbB2 is a promising biomarker candidate for PD. In addition, lapatinib, an ErbB2 tyrosine kinase inhibitor, was used to verify this PD biomarker candidate in vivo. We found that lapatinib-attenuated dopaminergic neuron loss and PD-like behavior in the zebrafish PD model. Accordingly, the expression of ErbB2pY-1248 significantly increased in the MPTP-induced mouse PD model. Our results suggest that ErbB2pY-1248 is a predictive biomarker for PD. In this study, we found that ErbB2pY-1248 is a predictive biomarker of PD by using RPPA technology and in vivo verification. It offers a new perspective on PD diagnosing and treatment, which will be essential in identifying individuals at risk of PD. In addition, this study provides new ideas for digging into biomarkers of other neurodegenerative diseases.

Increased Serum S100β Concentration is Associated with Depression in Parkinson's Disease.

To explore the relationship between the serum level of S100 calcium-binding protein, beta chain (S100β) and Parkinson's disease (PD) with depression. A total of 145 patients with PD and 60 healthy controls matched for sex, age, and years of education in our hospital were selected. Fluorescence quantitative immunochromatography was used to quantify the level of S100β in serum. Clinical manifestations were assessed by Unified Parkinson's Disease Rating Scale part-III (UPDRS-III), Hoehn & Yahr (H-Y) stage and 17-item Hamilton Rating Scale for Depression (HAMD-17). According to the results of HAMD-17, PD patients were divided into PD with depression group and PD without depression group. The relationship between serum S100β and HAMD-17 scores in PD patients with depression was investigated through correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum S100β. The level of serum S100β in PD with depression group was significantly higher than that in PD without depression group and control group. In PD patients with depression, serum S100β level was positively correlated with UPDRS-III score, H-Y Scale and HAMD-17 score. The HAMD-17 score was positively correlated with the UPDRS-III and H-Y scales, and the increase in the HAMD-17 score was associated with women. Elevated serum S100β level and UPDRS-III score are independent risk factors for PD with depression. Analysis of receiver operating characteristic (ROC) curves showed that the serum S100β level with a cutoff of 0.28 ng/mL distinguished patients with PD with or without depression with an area under the ROC curve (AUC) of 0.742, sensitivity of 0.696, and specificity of 0.779. The serum S100β level could be a biomarker of PD with depression.

Meta-analysis to Implement Alpha-Synuclein in Extracellular Vesicles as a Potential Biomarker for Parkinsons Disease.

Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.

Non-invasive Monitoring of α-Synuclein in Saliva for Parkinson's Disease Using Organic Electrolyte-Gated FET Aptasensor.

Parkinson's disease (PD) currently affects more than 1 million people in the US alone, with nearly 8.5 million suffering from the disease worldwide, as per the World Health Organization. However, there remains no fast, pain-free, and effective method of screening for the disease in the ageing population, which also happens to be the most susceptible to this neurodegenerative disease. αSynuclein (αSyn) is a promising PD biomarker, demonstrating clear delineations between levels of the αSyn monomer and the extent of αSyn aggregation in the saliva of PD patients and healthy controls. In this work, we have demonstrated a laboratory prototype of a soft fluidics integrated organic electrolyte-gated field-effect transistor (OEGFET) aptasensor platform capable of quantifying levels of αSyn aggregation in saliva. The aptasensor relies on a recently reported synthetic aptamer which selectively binds to αSyn monomer as the bio-recognition molecule within the integrated fluidic channel of the biosensor. The produced saliva sensor is label-free, fast, and reusable, demonstrating good selectivity only to the target molecule in its monomer form. The novelty of these devices is the fully isolated organic semiconductor, which extends the shelf life, and the novel fully integrated soft microfluidic channels, which simplify saliva loading and testing. The OEGFET aptasensor has a limit of detection of 10 fg/L for the αSyn monomer in spiked saliva supernatant solutions, with a linear range of 100 fg/L to 10 μg/L. The linear range covers the physiological range of the αSyn monomer in the saliva of PD patients. Our biosensors demonstrate a desirably low limit of detection, an extended linear range, and fully integrated microchannels for saliva sample handling, making them a promising platform for non-invasive point-of-care testing of PD.

No Correlation between Plasma GPNMB Levels and Multiple System Atrophy in Chinese Cohorts.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD. The goal of this study was to investigate whether plasma GPNMB could act as a potential biomarker for the clinical diagnosis and severity monitoring of multiple system atrophy (MSA), another typical synucleinopathy. Plasma GPNMB levels in patients with MSA, patients with PD, and healthy control subjects (HCs) were quantified using enzyme-linked immunosorbent assays. A total of 204 patients with MSA, 65 patients with PD, and 207 HCs were enrolled. The plasma GPNMB levels in patients with MSA were similar to those in HCs (P = 0.251) but were significantly lower than those in patients with PD (P = 0.003). Moreover, there was no significant correlation detected between the plasma GPNMB levels and disease severity scores of patients with MSA. No evidence was detected for the biomarker potential of plasma GPNMB in MSA. © 2023 International Parkinson and Movement Disorder Society.

Exaggerated High-Beta Oscillations are Associated with Cortical Thinning at the Motor Cortex in Parkinson's Disease.

Elevated β oscillations (13-35 Hz) are characteristic pathophysiology in Parkinson's Disease (PD). Cortical thinning has also been reported in the disease, however the relationship between these biomarkers of PD has not been established. By comparing electrophysiological measurements with cortical thickness, this study aims to reveal the pathoetiology of disease and symptoms in PD. Preoperative magnetic resonance imaging (MRI) and intraoperative local field potentials (LFPs) were collected from 34 subjects diagnosed with PD. Cortical surfaces were reconstructed from the images, and cortical thickness was extracted from the subregions where the recording electrode was placed in M1. LFPs were preprocessed and cleaned using a semiautomatic artifact detection algorithm, then power spectral densities (PSD) were computed and periodic and aperiodic frequency components were calculated. Nonparametric Spearman rank correlations assessed the relationship between electrophysiological components (i.e. center frequency (CF), power, bandwidth, 1/f exponent, knee), with cortical thickness. According to the CF of each subject's PSD, the cohort was split into two sub-groups: low-β peak (13-20 Hz) and high-β peak (20-35 Hz) groups. There was a significant negative correlation between power and cortical thickness only in the high-β subgroup (r=-0.48, p(corrected)=0.049). This relationship remained significant when correcting for age (r=-0.52,p=0.015), indicating that the effect of age on cortical thinning was not the determining factor. We did not find significant differences between UPDRS-III motor symptom scores for the low-and high-β subgroups. Of note is the dominance of high-β oscillatory power and its relationship with cortical thickness. As suggested by the literature, increased high-β activity during movement may be exaggerated in PD. These findings suggest that the characteristic cortical thinning in PD causes variation in electrical activity, leading to elevated high-β activity.Clinical relevance- This multimodal study provides additional insights on the pathophysiology and its relevance with morphology of Parkinson's Disease.

Extracellular Vesicles for the Diagnosis of Parkinson's Disease: Systematic Review and Meta-Analysis.

Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, and monitoring therapeutic response). Imaging, genetic, and biochemical biomarkers have been widely studied. In recent years, extracellular vesicles (EVs) have become a promising material for biomarker development. Proteins and molecular material from any organ, including the central nervous system, can be packed into EVs and transported to the periphery into easily obtainable biological specimens like blood, urine, and saliva. We performed a systematic review and meta-analysis of articles (published before November 15, 2022) reporting biomarker assessment in EVs in PD patients and healthy controls (HCs). Biomarkers were analyzed using random effects meta-analysis and the calculated standardized mean difference (Std.MD). Several proteins and ribonucleic acids have been identified in EVs in PD patients, but only α-synuclein (aSyn) and leucine-rich repeat kinase 2 (LRRK2) were reported in sufficient studies (n = 24 and 6, respectively) to perform a meta-analysis. EV aSyn was significantly increased in neuronal L1 cell adhesion molecule (L1CAM)-positive blood EVs in PD patients compared to HCs (Std.MD = 1.84, 95% confidence interval = 0.76-2.93, P = 0.0009). Further analysis of the biological sample and EV isolation method indicated that L1CAM-IP (immunoprecipitation) directly from plasma was the best isolation method for assessing aSyn in PD patients. Upcoming neuroprotective clinical trials immediately need peripheral biomarkers for identifying individuals at risk of developing PD. Overall, the improved sensitivity of assays means they can identify biomarkers in blood that reflect changes in the brain. CNS-derived EVs in blood will likely play a major role in biomarker development in the coming years. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Absolute quantification of neuromelanin in formalin-fixed human brains using absorbance spectrophotometry.

Parkinson's disease is characterised by a visual, preferential degeneration of the pigmented neurons in the substantia nigra. These neurons are pigmented by neuromelanin which decreases in Parkinson's disease. Not much is known about NM as it is difficult to study and quantify, primarily due to its insolubility in most solvents except alkali. Neuromelanin quantification could progress the development of biomarkers for prodromal Parkinson's disease and provide insights into the presently unclear role of neuromelanin in Parkinson's disease aetiology. Light microscopy with stereology can visualise pigmented neurons, but it cannot quantify neuromelanin concentrations. Absolute neuromelanin quantification using absorbance spectrophotometry is reported in the literature, but the methodology is dated and only works with fresh-frozen tissue. We have developed a quantification protocol to overcome these issues. The protocol involves breakdown of fixed tissue, dissolving the tissue neuromelanin in sodium hydroxide, and measuring the solution's 350 nm absorbance. Up to 100 brain samples can be analysed in parallel, using as little as 2 mg of tissue per sample. We used synthetic neuromelanin to construct the calibration curve rather than substantia nigra neuromelanin. Our protocol enzymatically synthesises neuromelanin from dopamine and L-cysteine followed by high-heat ageing. This protocol enables successful lysis of the fixed substantia nigra tissue and quantification in three brains, with neuromelanin concentrations ranging from 0.23-0.55 μg/mg tissue. Quantification was highly reproducible with an interassay coefficient of variation of 6.75% (n = 5). The absorbance spectra and elemental composition of the aged synthetic neuromelanin and substantia nigra neuromelanin show excellent overlap. Our protocol can robustly and reliably measure the absolute concentration of neuromelanin in formalin-fixed substantia nigra tissue. This will enable us to study how different factors affect neuromelanin and provide the basis for further development of Parkinson's disease biomarkers and further research into neuromelanin's role in the brain.

Salivary Biomarkers: Noninvasive Ways for Diagnosis of Parkinson's Disease.

Finding reliable biomarkers has a crucial role in Parkinson's disease (PD) assessments. Saliva is a bodily fluid, which might be used as a source of biomarkers for PD. Our article has reviewed several publications on salivary proteins in PD patients and their potential as biomarkers. We find out that α-Syn's proportion in oligomeric form is higher in PD patients' saliva, which is potent to use as a biomarker for PD. The salivary concentration of DJ-1 and alpha-amylase is lower in PD patients. Also, substance P level is more moderate in PD patients. Although salivary flow rate is decreased in PD patients, high levels of heme oxygenase and acetylcholinesterase might be used as noninvasive biomarkers. Salivary miRNAs (miR-153, miR-223, miR-874, and miR-145-3p) are novel diagnostic biomarkers that should be given more attention.

WITHDRAWN: Association between regular physical activity and biomarker changes in early Parkinson's disease patients

Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid β (Aβ), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. This retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. Regular physical activity was associated with a slower decline of DAT uptake in the caudate (β=0.063, p=0.011) and the putamen (β=0.062, p=0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. Regular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

Detection of a Parkinson's Disease-Specific MicroRNA Signature in Nasal and Oral Swabs.

Biomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions. We have previously identified a PD-specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes α-synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. Healthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real-time polymerase chain reaction. Statistical analysis revealed a significantly increased expression of hsa-miR-1260a in cases who had PD. Interestingly, hsa-miR-1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa-miR-1260a segregated to Golgi-associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa-miR-1260a target gene expression was reduced in iRBD and PD groups. Our work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays.

Even though it is currently well-established that α-synuclein aggregation is closely associated with the pathological events in Parkinson's disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between α-synuclein aggregates and the onset and progression of neurodegeneration in these diseases remain unclear. The process of aggregation initiates from a structurally distorted monomer that gradually oligomerizes to generate a repertoire of fibrillar and oligomeric multimers that deposit within diseased cells in the brain. Total α-synuclein has been proposed as a potential biomarker in PD, but most of the studies do not discriminate between distinct α-synuclein conformers. To correlate protein measurements to disease pathology, we have developed a conformation-specific ELISA method that selectively detects fibrillar and oligomeric forms of α-synuclein without cross-reacting with monomers. We have used this assay to determine the levels of aggregated α-synuclein in human and mouse brain tissue as well as in CSF and CSF-derived exosomes from patients with synucleinopathy and control subjects. Our results verify the ability of the new assay to detect aggregated α-synuclein in complex matrices and support the idea that the levels of these conformers are related to the age of onset in PD patients, while CSF analysis showed that these species exist in low abundance in CSF and CSF-derived exosomes. Future studies will be required to fully assess the diagnostic usefulness of this ELISA in synucleinopathies.