Parkinson's Disease Patients Research Articles

Systematic assessment of square-wave jerks in progressive supranuclear palsy: a video-oculographic study

BackgroundThe presence of frequent macro-square-wave jerks (SWJs) has been recently included in the diagnostic criteria for progressive supranuclear palsy (PSP). The aim of the current video-oculographic study was to systematically assess the presence and features of SWJs during a brief fixation task in PSP, in comparison with Parkinson’s disease (PD) patients and healthy controls (HC).MethodsThirty-eight PSP patients, 55 PD patients and 40 HC were enrolled in the study. All patients underwent a video-oculographic (VOG) examination including a 5-s fixation task, and the number, duration and amplitude of SWJs were recorded. The diagnostic performance of several SWJs parameters were then compared in distinguishing PSP from PD patients and controls.ResultsPSP patients showed a higher number and amplitude of SWJs compared to PD patients and controls. At least two SWJs within the 5-s fixation task were observed in 81.6% of PSP patients, 52.7% of PD patients and 25% of HC. The SWJs amplitude was the parameter showing the highest performances in distinguishing PSP from PD (AUC: 0.78) and HC (AUC: 0.88), outperforming the SWJ number and duration. The SWJ amplitude was larger in PSP-Richardson’s syndrome than in PSP-Parkinsonism patients, while no difference was found between PSP patients with different degrees of vertical ocular motor dysfunction.ConclusionsThis video-oculographic study provides robust evidence of larger SWJs number and amplitude in PSP than in PD patients, with some potential for differential diagnosis, supporting the inclusion of this ocular sign in PSP criteria.

Professor ZHUANG Lixing's experience of integrated acupuncture and medication approach to treat motor complications in Parkinson's disease based on the alternation of "movement and stillness"

This paper introduces Professor ZHUANG Lixing's experience in treating motor complications of Parkinson's disease (PD) with acupuncture combined with medication. Based on the characteristics of the alternation of "movement and stillness" in PD motor complications, Professor ZHUANG divides these complications into three distinct periods: "movement" stage, "stillness" stage and "alternation" stage, and proposes an integrated approach of acupuncture and medication, with staged treatment tailored to each period. The main acupoints include Jin's three needles to regulate spirit (four spirit needles, Shenting [GV 24], Yintang [GV 24+], Shenmen [HT 7], Sanyinjiao [SP 6]), along with hand tremor three needles (Hegu [LI 4], Quchi [LI 11], Dingchan), foot tremor three needles (Yinlingquan [SP 9], Yanglingquan [GB 34], Taichong [LR 3]), and Du's three needles (Dazhui [GV 14], Jinsuo [GV 8], Mingmen [GV 4]). The primary medicinal formulas include Lingjiao Gouteng decoction, Banxia Baizhu Tianma decoction, Bazhen decoction combined with Buzhong Yiqi decoction, Sini decoction combined with Yougui pills, and Xiaochaihu decoction. This integrated approach effectively alleviates the motor symptom fluctuations in PD patients, helping them maintain a stable life.

Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson's Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids.

Recent insights into Parkinson's disease (PD), a progressive neurodegenerative disorder, suggest a significant influence of the gut microbiome on its pathogenesis and progression through the gut-brain axis. This study integrates 16S rRNA sequencing, high-throughput transcriptomic sequencing, and animal model experiments to explore the molecular mechanisms underpinning the role of gut-brain axis in PD, with a focus on short-chain fatty acids (SCFAs) mediated by the SCFA receptors FFAR2 and FFAR3. Our findings highlighted prominent differences in the gut microbiota composition between PD patients and healthy individuals, particularly in taxa such as Escherichia_Shigella and Bacteroidetes, which potentially impact SCFA levels through secondary metabolite biosynthesis. Notably, fecal microbiota transplantation (FMT) from healthy to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models significantly improved motor function, enhanced dopamine and serotonin levels in the striatum, and increased the number of dopaminergic neurons in the substantia nigra while reducing glial cell activation. This therapeutic effect was associated with increased levels of SCFAs such as acetate, propionate, and butyrate in the gut of MPTP-lesioned mice. Moreover, transcriptomic analyses revealed upregulated expression of FFAR2 and FFAR3 in MPTP-lesioned mice, indicating their crucial role in mediating the benefits of FMT on the central nervous system. These results provide compelling evidence that gut microbiota and SCFAs play a critical role in modulating the gut-brain axis, offering new insights into PD's etiology and potential targets for therapeutic intervention.

Sleep disorders and Parkinson's disease: is there a right direction?

In the last years, the hypothesis of a close relationship between sleep disorders (SDs) and Parkinson's disease (PD) has significantly strengthened. Whether this association is causal has been also highlighted by recent evidence demonstrating a neurobiological link between SDs and PD. Thus, the question is not whether these two chronic conditions are mutually connected, but rather how and when this relationship is expressed. Supporting this, not all SDs manifest with the same temporal sequence in PD patients. Indeed, SDs can precede or occur concomitantly with the onset of the clinical manifestation of PD. This review discusses the existing literature, putting under a magnifying glass the timing of occurrence of SDs in PD-neurodegeneration. Based on this, here, we propose two possible directions for studying the SDs-PD relationship: the first direction, from SDs to PD, considers SDs as potential biomarker/precursor of future PD-neurodegeneration; the second direction, from PD to SDs, considers SDs as concomitant symptoms in manifest PD, mainly related to primary PD-neuropathology and/or parkinsonian drugs. Furthermore, for each direction, we questioned SDs-PD relationship in terms of risk factors, neuronal circuits/mechanisms, and impact on the clinical phenotype and disease progression. Future research is needed to investigate whether targeting sleep may be the winning strategy to treat PD, in the context of a personalized precision medicine.

Serum Levels of Plasminogen Activator Inhibitor-1 in Patients with Parkinson's Disease.

To investigate serum plasminogen activator inhibitor-1 (PAI-1) levels of patients with Parkinson's disease (PD) and their relationship with clinical findings and treatment of disease. The study included 125 PD patients and 48 healthy controls. Patients have been taking effective dopaminergic treatment regularly. The clinical severity of parkinsonism was assessed using the Hoehn and Yahr (HY) staging scale and Unified PD Rating Scale (UPDRS). PAI-1 level analysis was performed by enzyme-linked immunosorbent assay. Patients with PD had significantly lower serum PAI-1 levels than healthy controls (p < 0.001). Correlations with clinical findings showed only marginally positive correlation between serum PAI-1 and HY score (r = 0.170, p = 0.05). In contrast, no significant correlation was demonstrated with the UPDRS score or other clinical parameters. This is the first comprehensive analysis of serum PAI-1 levels in patients with PD. The distribution of PAI-1 in PD appears to be complex. The study results implicate that the paradoxical effects of tissue plasminogen activator on the brain parenchyma can be important in the pathophysiology of PD. Future studies are needed to elucidate the role of fibrinolytic system components in PD.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. Our goal was to investigate the effects of genetic variants on risk and time to LID. We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21-2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09-1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile = 1.27; 95% CI, 1.03-1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile = 1.38; 95% CI, 1.07-1.79; P = 0.0128; HRfourth_quartile = 1.38; 95% CI = 1.06-1.78; P = 0.0147). This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Serum cholesterol levels and Parkinson’s disease: a detailed investigation in Turkish population

ABSTRACT Objectives Parkinson’s disease (PD) involves the progressive loss of dopaminergic neurons and the accumulation of α-synuclein. Elevated cholesterol levels may exacerbate α-synuclein aggregation, potentially contributing to PD. This study investigates the link between lipid profiles and PD severity, as well as cognitive functions in patients, aiming to inform pathogenesis and management strategies. Methods Data from 250 PD patients and 100 healthy controls were analyzed. Serum cholesterol levels were compared with disease severity using Unified Parkinson’s Disease Rating Scale (UPDRS) and modified Hoehn & Yahr Rating Scale (mH&Y). Mini-Mental State Examination (MMSE) assessed cognitive functions. Results Of the participants, 45.4% were female, 54.6% male, with a mean age of 69.09 ± 11.13 years. Mean UPDRS score was 52.34 ± 26.32, mH&Y was 2.28 ± 0.91. Patients had significantly higher HDL levels (47.92 ± 11.63) than controls (45.40 ± 13.89) (p = 0.024). HDL levels were significantly higher in patients with cognitive impairment than in patients with cognitive normal (p = 0.004). On the contrary, triglyceride levels were significantly lower in those with cognitive impairment compared to those with cognitively normal (p = 0.005). Multivariate logistic regression showed being male associated with 3.796 times higher risk of illness, and HDL is associated with 1.030 times increased illness risk. Conclusion High HDL levels and male gender particularly increase the risk of Parkinson’s disease. Additionally, HDL and triglyceride levels affect the cognition of PD patients. Further studies on the impact of cholesterol metabolism on the pathogenesis of PD could contribute to identifying effective treatment targets.

TECHNOLOGY-BASED EVALUATION IN PARKINSONISM

Parkinson's disease is a neurodegenerative disorder characterized by motor and non-motor symptoms that worsen over time. Today, traditional clinical assessment methods are used to monitor disease progression and evaluate treatment responses. However, these methods are subjective and may fail to measure specific conditions. In recent years, thanks to advances in wearable technologies, smart sensors, and data analysis, technology-based approaches to the assessment of patients with Parkinson's disease have gained more attention. With these technologies, objective data can be obtained by monitoring patients' daily activities, motor functions, and symptoms. Motor symptoms such as tremor severity, rigidity, bradykinesia, postural instabilities, freezing phenomenon, and motor parameters of speech impairment can be objectively measured through these technologies. Furthermore, the ability to remotely transmit these data allows patients to be assessed in their own homes and provides continuous feedback to healthcare professionals. This review highlights the importance and potential of technology-based assessment methods in Parkinson's patients and aims to guide future research.

Surgicogenomics: The Role of Genetics in Deep Brain Stimulation in Parkinson's Disease Patients.

Parkinson's disease (PD) is the second-most common neurodegenerative disease, affecting 1% of people aged over 60. Currently, there is only symptomatic relief for PD patients, with levodopa being the gold standard of PD treatment. Deep brain stimulation (DBS) is a surgical option to treat PD patients. DBS improves motor functions and may also allow a significant reduction in dopaminergic medication. Important parameters for DBS outcomes are the disease duration, the age of disease onset, responsiveness to levodopa and cognitive or psychiatric comorbidities. Emerging data also highlight the need to carefully consider the genetic background in the preoperative assessment of PD patients who are candidates for DBS, as genetic factors may affect the effectiveness of DBS in these patients. This review article discusses the role of genetics in DBS for PD patients, in an attempt to better understand inter-individual variability in DBS response, control of motor PD symptoms and appearance of non-motor symptoms, especially cognitive decline.

Levodopa Sensing in Human Sweat Using 3D Printed Sensors and a Smartphone

Parkinson’s disease (PD) is one of the leading neurological disorders negatively impacting health on a global scale. Patients diagnosed with PD require frequent monitoring, prescribed medications, and therapy for extended periods as symptom severity worsens. The primary pharmaceutical treatment for PD patients is levodopa (L-Dopa) which reduces many symptoms experienced by PD patients (e.g., tremors, cognitive ability, motor dysfunction, etc.) through the regulation of dopamine levels in the body. Herein, the first detection of L-Dopa in human sweat using a low-cost 3D printed sensor with a simple and rapid fabrication protocol combined with a portable potentiostat wirelessly connected to a smartphone via Bluetooth is discussed. By combining saponification and electrochemical activation into a single protocol, the optimized 3D printed carbon electrodes were able to simultaneously detect uric acid and L-Dopa throughout their biologically relevant ranges. The optimized sensors provided a sensitivity of 83 + 3 nA/µM from 24 µM to 300 nM L-Dopa. Common physiological interferents found in sweat (e.g., ascorbic acid, glucose, caffeine) showed no influence on the response for L-Dopa. Lastly, a percent recovery of L-Dopa in human sweat using a smartphone-assisted handheld potentiostat resulted in the recovery of 100 + 8 %, confirming the ability of this sensor to accurately detect L-Dopa in sweat.

Fractional Anisotropy is a More Sensitive Diagnostic Biomarker Than Mean Kurtosis for Patients with Parkinson Disease with Cognitive Dysfunction: A Diffusional Kurtosis Map Tract-Based Spatial Statistics Study.

There is heterogeneity of white matter damage in Parkinson's disease patients with different cognitive states. Our aim was to find sensitive diffusional kurtosis imaging biomarkers to differentiate the white matter damage pattern of mild cognitive impairment and dementia. Nineteen patients with Parkinson disease with mild cognitive impairment and 18 patients with Parkinson disease with dementia were prospectively enrolled. All participants underwent MR examination with 3D-T1-weighted image and diffusional kurtosis imaging sequences. Demographic data were compared between the 2 groups. Voxelwise statistical analyses of diffusional kurtosis imaging parameters were performed using tract-based spatial statistics. The receiver operator characteristic curve of significantly different metrics was graphed. The correlation of significantly different metrics with global cognitive status was analyzed. Compared with the Parkinson disease with mild cognitive impairment group, the fractional anisotropy and mean kurtosis values decreased in 4 independent clusters in the forceps minor, forceps major, inferior fronto-occipital fasciculus, and the inferior and superior longitudinal fasciculus in patients with Parkinson disease with dementia; the mean diffusivity decreased in 1 cluster in the forceps minor. The fractional anisotropy value in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus would be the diffusional kurtosis imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and patients with Parkinson disease with dementia, with the best diagnostic efficiency of 0.853. The fractional anisotropy values in the forceps minor (β = 84.20, P < .001) and years of education (β = 0.38, P = .014) were positively correlated with the Montreal Cognitive Assessment. The diffusional kurtosis imaging-derived fractional anisotropy and mean kurtosis can detect the different white matter damage patterns of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia. Fractional anisotropy is more sensitive than mean kurtosis in the differential diagnosis; fractional anisotropy derived from diffusional kurtosis imaging could become a promising imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia.

The impact of combined aerobic and resistance exercise on the prognosis of early Parkinson's disease patients.

Although literature suggests that exercise can improve symptoms in Parkinson's Disease (PD) patients, research on the effects of aerobic exercise and resistance training (AE&RT) in early-stage PD remains limited. Understanding the synergistic effects of these exercise modalities can provide valuable insights for optimizing exercise interventions for PD patients, particularly in the early stages of the disease, where interventions may have the greatest impact on long-term functional outcomes. This study aimed to investigate the effects of a combined AE&RT program on motor function, postural stability, and cognitive processing speed in early stage PD patients. A total of 236 participants with early-stage PD were assigned to either the Aerobic Exercise Group (AE group) (n= 112) or the AE&RT Group (n= 124) inthis controlled randomized trial. The study employed a one-year supervised exercise program, with the AE Group participating in aerobic activities and the AE&RT Group engaging in combined AE&RT. Outcome measures included symptom improvement, motor function, postural stability, cognitive processing speed, peak oxygen consumption, quality of life evaluation, and the incidence of adverse events. The AE&RT Group demonstrated greater improvements in tremor, muscle rigidity, gait instability, sleep problems, and hyposmia compared to the AE Group. Additionally, the combined exercise group exhibited better cognitive processing speed, as well as enhanced motor function and postural stability. Peak oxygen consumption was significantly higher in the AE&RT Group. However, the quality of life evaluation indicated a statistically higher quality of life in the AE Group. There was no significant difference in the incidence of adverse events between the two groups. The findings suggest that the integration of AE&RT in early-stage PD patients leads to more comprehensive improvements in motor symptoms, cognitive function, postural stability, and cardiovascular fitness compared to aerobic exercise alone. These results have important implications for developing tailored exercise interventions to enhance the physical and cognitive well-being of individuals with early-stage PD.

Cortical morphological alterations in cognitively normal Parkinson’s disease with severe hyposmia

Olfactory dysfunction is a common non-motor symptom of Parkinson’s disease(PD) and may hold valuable insights into the disease’s underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients’ right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD’s pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

2341 Qualitative assessment of introducing bone health assessment for Parkinson’s disease patients in a university hospital setting

Abstract Introduction Parkinson’s disease (PD) patients with or without psychosis are at higher risk of recurrent falls and fracture and, as a consequence, higher mortality and morbidity NICE (13) Henderson et al. (2019). We conducted a qualitative study to understand barriers and facilitators of introducing ‘bone health assessment’ for PD patients. Method We conducted a pilot study to identify and implement a bone health assessment tool to communicate falls and fracture risks to GPs. • SWOT and Stakeholder analysis was conducted to identify an appropriate bone health assessment tool. • PDSA cycles were completed to assess barriers and facilitators of bone health assessment in all PD clinical areas. • 4 Participants were identified from all possible PD clinical settings and trained on how to use the FRAX assessment tool. • Semi structured interviews were conducted to explore themes from 6-week pilot study. Results Bone health assessments were not conducted routinely in PD clinical settings in our Trust Literature review/SWOT and Stake holder analysis identified ‘FRAX’ score as an appropriate bone health assessment tool for PD patients. Interviews with participants identified time constraints during the clinical consultation as a major barrier to conducting bone health assessment using the FRAX assessment tool. All participants agreed that this improved communication with patients and GPs in understanding bone health and risk of falls and fractures. Face to face PD Nurse Clinics were deemed the most appropriate clinical settings for these assessments. Conclusion As a result of this service improvement project bone health is now assessed in all PD Nurse clinics. This has enabled GPs to start the most appropriate bone protection treatment for PD patients.

Contrastive machine learning reveals Parkinson’s disease specific features associated with disease severity and progression

Parkinson’s disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

Clinically established early Parkinson's disease patients do not show impaired use of priors in conditions of perceptual uncertainty

The ability to use past learned experiences to guide decisions is an important component of adaptive behavior, especially when decision-making is performed under time pressure or when perceptual information is unreliable. Previous studies using visual discrimination tasks have shown that this prior-informed decision-making ability is impaired in Parkinson's disease (PD), but the mechanisms underlying this deficit and the precise impact of dopaminergic denervation within cortico-basal circuits remain unclear. To shed light on this problem, we evaluated prior-informed decision-making under various conditions of perceptual uncertainty in a sample of 13 clinically established early PD patients, and compared behavioral performance with healthy control (HC) subjects matched in age, sex and education. PD patients and HC subjects performed a random dot motion task in which they had to decide the net direction (leftward vs. rightward) of a field of moving dots and communicate their choices through manual button presses. We manipulated prior knowledge by modulating the probability of occurrence of leftward vs. rightward motion stimuli between blocks of trials, and by explicitly giving these probabilities to subjects at the beginning of each block. We further manipulated stimulus discriminability by varying the proportion of dots moving coherently in the signal direction and speed-accuracy instructions. PD patients used choice probabilities to guide perceptual decisions in both speed and accuracy conditions, and their performance did not significantly differ from that of HC subjects. An additional analysis of the data with the diffusion decision model confirmed this conclusion. These results suggest that the impaired use of priors during visual discrimination observed at more advanced stages of PD is independent of dopaminergic denervation, though additional studies with larger sample sizes are needed to more firmly establish this conclusion.

Application of EXODUS system combined with allosteric DNA nanoswitches in the detection of miR-107 among plasma exosomes of Parkinson's disease patients

This study aimed to achieve rapid detection of Parkinson's disease (PD) plasma exosome miR-107. A case-control design was used to collect ten Parkinson's disease and ten healthy control plasma samples from the Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from December 2023 to January 2024. Exosome detection via the ultrafast-isolation system (EXODUS) was used to isolate plasma exosomes. The nanoparticle tracking analysis technology and electron microscopy were used to identify exosome particle size and morphology. The Qiagen miRNeasy Micro Kit was used to extract RNA. The microRNA-activated conditional looping of engineered switches (miRacles) was used to detect miR-107, and the relative expression was analyzed by agarose gel electrophoresis. Thermo Fisher RevertAid RT Reverse Transcription Kit was used to perform reverse transcription of RNA, and real-time PCR was used to detect miR-107. The independent samples t-test was used for comparison between groups. EXODUS system completed the isolation of exosomes from 500 μl plasma within 1.5 hours. The exosome concentration (mean±SD) was (4.82±2.02)×1010 particles/ml in the control group and (5.08±2.34)×1010 particles/ml in the PD group. There was no significant difference in exosome concentration between PD patients and healthy controls (t=-0.168, P=0.872). The morphology of exosomes was confirmed by electron microscopy. The miRacles nanoswitch could detect fM-level miR-107 and also effectively distinguish miR-107 from its family members, including miR-15a and miR-16. Agarose gel electrophoresis showed that the mean±SD of relative grey value content was 1.00±0.26 in the control group and 1.86±0.21 in the PD group. The miR-107 in the PD group was significantly higher than that in the control (t=-8.143, P<0.001), which was consistent with the result of real-time PCR. EXODUS combined with miRacles could achieve rapid, non-enzymatic and cheap detection of plasma exosomal miR-107 in PD patients.

Causal associations between Helicobacter Pylori infection and the risk and symptoms of Parkinson's disease: a Mendelian randomization study.

Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; β = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.

Human perception of Parkinson's disease body odor in comparison to the volatile organic compounds of Parkinson's disease

IntroductionPatients with Parkinson's Disease (PD) have a distinctive body odor, which was first described by a patient's wife as musky and strong. Later analysis of sebum of patients with PD revealed four volatile organic compounds (VOC) (perillic aldehyde, hippuric acid, eicosane, octadecanal), that differed from healthy subjects, and the patient's wife confirmed that three of them smelled like patients with PD. However, it is unclear whether other people can also perceive this PD body odor and whether it can be artificially recreated. Hence, we aimed to systematically assess whether young women can perceive the PD body odor and whether they can discriminate between the PD body odor and the “artificial PD odor” composed of the four VOCs mentioned above. MethodsT-shirts were collected from 19 people with idiopathic PD and 15 age- and gender-matched healthy participants to represent the PD body odor and the healthy body odor, respectively. The four VOCs were diluted in 1,2-propanediol to prepare the artificial PD body odor. Body odors were rated by 26 young women. ResultsPD body odor was perceived as more musty, strong, smelly, and unpleasant compared to healthy and artificial PD body odor. Furthermore, around 80 % of women were able to discriminate PD body odor from artificial PD body odor. ConclusionOverall, this study confirmed a distinctive body odor quality of patients with PD, which can be perceived by young women. However, the four VOCs, composing the artificial PD body odor, were insufficient to reproduce the body odor from PD patients.

PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson’s disease

TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson’s disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5’-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.