NPJ Parkinson's Disease最新文献

Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial 帕金森病个性化治疗自适应 DBS 算法（ADAPT-PD）临床试验的传感数据和方法论

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-17 DOI: 10.1038/s41531-024-00772-5

Scott Stanslaski, Rebekah L. S. Summers, Lisa Tonder, Ye Tan, Michelle Case, Robert S. Raike, Nathan Morelli, Todd M. Herrington, Martijn Beudel, Jill L. Ostrem, Simon Little, Leonardo Almeida, Adolfo Ramirez-Zamora, Alfonso Fasano, Travis Hassell, Kyle T. Mitchell, Elena Moro, Michal Gostkowski, Nagaraja Sarangmat, Helen Bronte-Stewart

{"title":"Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial","authors":"Scott Stanslaski, Rebekah L. S. Summers, Lisa Tonder, Ye Tan, Michelle Case, Robert S. Raike, Nathan Morelli, Todd M. Herrington, Martijn Beudel, Jill L. Ostrem, Simon Little, Leonardo Almeida, Adolfo Ramirez-Zamora, Alfonso Fasano, Travis Hassell, Kyle T. Mitchell, Elena Moro, Michal Gostkowski, Nagaraja Sarangmat, Helen Bronte-Stewart","doi":"10.1038/s41531-024-00772-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00772-5","url":null,"abstract":"Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased sighing during sleep as a marker of multiple system atrophy 睡眠中叹息声增多是多系统萎缩的标志

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-16 DOI: 10.1038/s41531-024-00765-4

Estefania Vargas Gonzalez, Zhongmei Yang, Pauline Dodet, Smaranda Leu-Semenescu, Cécile Londner, Maxime Patout, Christian Straus, Thomas Similowski, David Grabli, Marie Vidailhet, Isabelle Arnulf

{"title":"Increased sighing during sleep as a marker of multiple system atrophy","authors":"Estefania Vargas Gonzalez, Zhongmei Yang, Pauline Dodet, Smaranda Leu-Semenescu, Cécile Londner, Maxime Patout, Christian Straus, Thomas Similowski, David Grabli, Marie Vidailhet, Isabelle Arnulf","doi":"10.1038/s41531-024-00765-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00765-4","url":null,"abstract":"Parkinson’s disease (PD) and multiple system atrophy (MSA) can be preceded by isolated REM sleep behavior disorder (iRBD). As excessive sighing during wakefulness is a red flag for MSA in individuals with parkinsonism, we measured sighing during slow wave sleep (N3) and REM sleep as potential biomarkers in 73 participants with MSA, 111 with iRBD, 257 with PD, and 115 controls. The number of sighs/hour of N3 (index) was higher in the MSA group than in the other groups. Sighs were rarer in REM sleep than in N3 sleep. A sigh index greater than 3.4/h of N3 was 95% sensitive in discriminating participants with MSA from controls, and a sigh index greater than 0.8 sigh/h of REM sleep was 87% specific in discriminating participants with MSA from controls. MSA participants with (vs. without) sigh were younger, had a lower apnea-hypopnea index (but no more stridor), and had no other difference in motor, autonomic, cognitive, and sensory symptoms. The sigh index could be used for screening for MSA in the millions of middle-aged persons who receive polysomnography for other purposes. Whether sighing in iRBD predicts preferential conversion towards MSA should be measured in a longitudinal study.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinico-physiological correlates of Parkinson’s disease from multi-resolution basal ganglia recordings 通过多分辨率基底神经节记录了解帕金森病的临床生理学相关性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-12 DOI: 10.1038/s41531-024-00773-4

Srdjan Sumarac, Jinyoung Youn, Conor Fearon, Luka Zivkovic, Prerana Keerthi, Oliver Flouty, Milos Popovic, Mojgan Hodaie, Suneil Kalia, Andres Lozano, William Hutchison, Alfonso Fasano, Luka Milosevic

{"title":"Clinico-physiological correlates of Parkinson’s disease from multi-resolution basal ganglia recordings","authors":"Srdjan Sumarac, Jinyoung Youn, Conor Fearon, Luka Zivkovic, Prerana Keerthi, Oliver Flouty, Milos Popovic, Mojgan Hodaie, Suneil Kalia, Andres Lozano, William Hutchison, Alfonso Fasano, Luka Milosevic","doi":"10.1038/s41531-024-00773-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00773-4","url":null,"abstract":"Parkinson’s disease (PD) has been associated with pathological neural activity within the basal ganglia. Herein, we analyzed resting-state single-neuron and local field potential (LFP) activities from people with PD who underwent awake deep brain stimulation surgery of the subthalamic nucleus (STN; n = 125) or globus pallidus internus (GPi; n = 44), and correlated rate-based and oscillatory features with UPDRSIII off-medication subscores. Rate-based single-neuron features did not correlate with PD symptoms. STN single-neuron and LFP low-beta (12–21 Hz) power and burst dynamics showed modest correlations with bradykinesia and rigidity severity, while STN spiketrain theta (4–8 Hz) power correlated modestly with tremor severity. GPi low- and high-beta (21–30 Hz) power and burst dynamics correlated moderately with bradykinesia and axial symptom severity. These findings suggest that elevated single-neuron and LFP oscillations may be linked to symptoms, though modest correlations imply that the pathophysiology of PD may extend beyond resting-state beta oscillations.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease 直立性低血压：帕金森病患者 "身体优先 "亚型的临床标记

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-11 DOI: 10.1038/s41531-024-00787-y

Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan

{"title":"Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease","authors":"Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan","doi":"10.1038/s41531-024-00787-y","DOIUrl":"https://doi.org/10.1038/s41531-024-00787-y","url":null,"abstract":"Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate 神经变性过程中的 GPR37 处理：帕金森病进展速度的潜在标志物

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-10 DOI: 10.1038/s41531-024-00788-x

Josep Argerich, Leonardo D. Garma, Marc López-Cano, Paula Álvarez-Montoya, Laura Gómez-Acero, Víctor Fernández-Dueñas, Ana B. Muñoz-Manchado, Ester Aso, Adam Boxer, Pol Andres-Benito, Per Svenningsson, Francisco Ciruela

{"title":"GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate","authors":"Josep Argerich, Leonardo D. Garma, Marc López-Cano, Paula Álvarez-Montoya, Laura Gómez-Acero, Víctor Fernández-Dueñas, Ana B. Muñoz-Manchado, Ester Aso, Adam Boxer, Pol Andres-Benito, Per Svenningsson, Francisco Ciruela","doi":"10.1038/s41531-024-00788-x","DOIUrl":"https://doi.org/10.1038/s41531-024-00788-x","url":null,"abstract":"The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The value of PET/CT in the diagnosis and differential diagnosis of Parkinson’s disease: a dual-tracer study PET/CT 在帕金森病诊断和鉴别诊断中的价值：一项双示踪剂研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-10 DOI: 10.1038/s41531-024-00786-z

Xiaoxiao Du, Hongguang Zhao, Yinghua Li, Yuyin Dai, Lulu Gao, Yi Li, Kangli Fan, Zhihui Sun, Ying Zhang

{"title":"The value of PET/CT in the diagnosis and differential diagnosis of Parkinson’s disease: a dual-tracer study","authors":"Xiaoxiao Du, Hongguang Zhao, Yinghua Li, Yuyin Dai, Lulu Gao, Yi Li, Kangli Fan, Zhihui Sun, Ying Zhang","doi":"10.1038/s41531-024-00786-z","DOIUrl":"https://doi.org/10.1038/s41531-024-00786-z","url":null,"abstract":"Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson’s disease (PD). This study aimed to evaluate the performance of PET/CT with 11C-2β-Carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. 11C-CFT and 18F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of 11C-CFT and 18F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on 11C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in 11C-CFT uptake. The areas under the curve (AUCs) for 11C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On 18F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that 11C-CFT and 18F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity α-突触核蛋白诱导的黑质变性和普拉克索治疗会破坏前额纹状体的可塑性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-09 DOI: 10.1038/s41531-024-00781-4

Sarah Chevalier, Mélina Decourt, Maureen Francheteau, François Nicol, Anaïs Balbous, Pierre-Olivier Fernagut, Marianne Benoit-Marand

{"title":"Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity","authors":"Sarah Chevalier, Mélina Decourt, Maureen Francheteau, François Nicol, Anaïs Balbous, Pierre-Olivier Fernagut, Marianne Benoit-Marand","doi":"10.1038/s41531-024-00781-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00781-4","url":null,"abstract":"Parkinson’s disease is characterized by the degeneration of substantia nigra pars compacta (SNc) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular and molecular adaptations following neurodegeneration or dopamine replacement therapy (DRT) have been described in motor networks but little is known regarding associative basal ganglia loops. This study investigated the contributions of nigrostriatal degeneration and pramipexole (PPX) on neuronal activity in the orbitofrontal cortex (OFC), frontostriatal plasticity, and markers of synaptic plasticity. Bilateral nigrostriatal degeneration was induced by viral-mediated expression of human mutated alpha-synuclein in the SNc. Juxtacellular recordings were performed in anesthetized rats to evaluate neuronal activity in the OFC. Recordings in the dorsomedial striatum (DMS) were performed, and spike probability in response to OFC stimulation was measured before and after high-frequency stimulation (HFS). Post-mortem analysis included stereological assessment of nigral neurodegeneration, BDNF and TrkB protein levels. Nigrostriatal neurodegeneration led to altered firing patterns of OFC neurons that were restored by PPX. HFS of the OFC led to an increased spike probability in the DMS, while dopaminergic loss had the opposite effect. PPX led to a decreased spike probability following HFS in control rats and failed to counteract the effect of dopaminergic neurodegeneration. These alterations were associated with decreased levels of BDNF and TrkB in the DMS. This study demonstrates that nigral dopaminergic loss and PPX both contribute to alter frontostriatal transmission, precluding adequate information processing in associative basal ganglia loops as a gateway for the development of non-motor symptoms or non-motor side effects of DRT.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uric acid and alterations of purine recycling disorders in Parkinson’s disease: a cross-sectional study 尿酸与帕金森病患者嘌呤循环障碍的改变：一项横断面研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-09 DOI: 10.1038/s41531-024-00785-0

Sayuri Shima, Yasuaki Mizutani, Junichiro Yoshimoto, Yasuhiro Maeda, Reiko Ohdake, Ryunosuke Nagao, Toshiki Maeda, Atsuhiro Higashi, Akihiro Ueda, Mizuki Ito, Tatsuro Mutoh, Hirohisa Watanabe

{"title":"Uric acid and alterations of purine recycling disorders in Parkinson’s disease: a cross-sectional study","authors":"Sayuri Shima, Yasuaki Mizutani, Junichiro Yoshimoto, Yasuhiro Maeda, Reiko Ohdake, Ryunosuke Nagao, Toshiki Maeda, Atsuhiro Higashi, Akihiro Ueda, Mizuki Ito, Tatsuro Mutoh, Hirohisa Watanabe","doi":"10.1038/s41531-024-00785-0","DOIUrl":"https://doi.org/10.1038/s41531-024-00785-0","url":null,"abstract":"The relationship between reduced serum uric acid (UA) levels and Parkinson’s disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (p < 0.0001; effect size r = 0.5007 in serum, p = 0.0046; r = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (p = 0.0002; r = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (p < 0.0001, r = 0.5396: p = 0.0276, r = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying potential causal effects of Parkinson’s disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank 确定帕金森病的潜在因果效应：英国生物库中基于多基因风险评分的全表型关联和亡羊补牢随机化研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-06 DOI: 10.1038/s41531-024-00780-5

Changhe Shi, Dongrui Ma, Mengjie Li, Zhiyun Wang, Chenwei Hao, Yuanyuan Liang, Yanmei Feng, Zhengwei Hu, Xiaoyan Hao, Mengnan Guo, Shuangjie Li, Chunyan Zuo, Yuemeng Sun, Mibo Tang, Chengyuan Mao, Chan Zhang, Yuming Xu, Shilei Sun

{"title":"Identifying potential causal effects of Parkinson’s disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank","authors":"Changhe Shi, Dongrui Ma, Mengjie Li, Zhiyun Wang, Chenwei Hao, Yuanyuan Liang, Yanmei Feng, Zhengwei Hu, Xiaoyan Hao, Mengnan Guo, Shuangjie Li, Chunyan Zuo, Yuemeng Sun, Mibo Tang, Chengyuan Mao, Chan Zhang, Yuming Xu, Shilei Sun","doi":"10.1038/s41531-024-00780-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00780-5","url":null,"abstract":"There is considerable uncertainty regarding the associations between various risk factors and Parkinson’s Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson’s Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation 帕金森病与 TET2 突变的克隆性造血有关

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-06 DOI: 10.1038/s41531-024-00784-1

Kyung Ah Woo, Han-Joon Kim, Chan Young Lee, Jung Hwan Shin, Choonghyun Sun, Hogune Im, Hongyul An, Jiwoo Lim, Su-Yeon Choi, Youngil Koh, Beomseok Jeon

{"title":"Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation","authors":"Kyung Ah Woo, Han-Joon Kim, Chan Young Lee, Jung Hwan Shin, Choonghyun Sun, Hogune Im, Hongyul An, Jiwoo Lim, Su-Yeon Choi, Youngil Koh, Beomseok Jeon","doi":"10.1038/s41531-024-00784-1","DOIUrl":"https://doi.org/10.1038/s41531-024-00784-1","url":null,"abstract":"Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson’s disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11–2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0