NPJ Parkinson's Disease最新文献_第4页

Automatic analysis of eyelid movement in de-novo Parkinson’s disease 新生帕金森病眼睑运动的自动分析

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-06 DOI: 10.1038/s41531-025-01021-z

Louis Kälble, Tereza Tykalova, David Zogala, Petr Dusek, Jan Rusz, Michal Novotny

{"title":"Automatic analysis of eyelid movement in de-novo Parkinson’s disease","authors":"Louis Kälble, Tereza Tykalova, David Zogala, Petr Dusek, Jan Rusz, Michal Novotny","doi":"10.1038/s41531-025-01021-z","DOIUrl":"https://doi.org/10.1038/s41531-025-01021-z","url":null,"abstract":"This study presents an automated, objective method for eyelid movement assessment in de-novo Parkinson’s disease(PD) using a one-dimensional camera setup during monologue. These measurements were related to Dopamine Transporter Single Photon Emission Tomography and clinical scores. State-of-the-art computer-vision technologies and deep-learning neural networks were utilized to measure fourteen eyelid movement markers describing blinking and eyelid kinematics. Video-recordings were collected from a total of 120 de-novo patients with PD and 55 healthy controls. Abnormal blinking was present in 38% of PD, indicated by a reduced blink rate (p < 0.001), an increased inter-blink interval (p < 0.001), and an increased rigidity of the palpebral aperture (p < 0.001). The classification experiment reached an area under the curve of 0.81 on a blinded test set. The blink rate correlated with the loss of nigral dopaminergic neurons (r = 0.35, p < 0.001). These findings suggest eyelid movement markers as strong reflections of striatal dopaminergic activity levels, underscoring the method’s potential as a reliable early PD biomarker.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"75 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237140","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

Effects of virtual reality on spatiotemporal gait parameters and freezing of gait in Parkinson’s disease 虚拟现实技术对帕金森病患者时空步态参数及步态冻结的影响

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-04 DOI: 10.1038/s41531-025-01017-9

Lei Ma, Bar Yosef, Ipek Talu, Daniel Batista, Emi Jenkens-Drake, Nanthia Suthana, Katy A Cross

引用次数: 0

New diagnostic and staging framework applied to established PD in the BioFIND cohort 新的诊断和分期框架应用于已建立的PD在BioFIND队列

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-04 DOI: 10.1038/s41531-025-00992-3

Marco J. Russo, Un Jung Kang

引用次数: 0

Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis 罗伊氏乳杆菌衍生的γ-氨基丁酸通过AKT-GSK3β-GPX4轴抑制铁下垂，减轻mptp诱导的帕金森病

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-04 DOI: 10.1038/s41531-025-01022-y

Xuechao Dong, Teng Yang, Zheng Jin

{"title":"Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson’s disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis","authors":"Xuechao Dong, Teng Yang, Zheng Jin","doi":"10.1038/s41531-025-01022-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01022-y","url":null,"abstract":"Parkinson’s disease (PD) is a debilitating neurological disorder characterized by motor dysfunction, which has been associated with alterations in the gut microbiota. Lactobacillus reuteri (L. reuteri), a safe and versatile probiotic, exhibits potent immunomodulatory functions and neuroprotective effects. However, the extent and mechanisms by which L. reuteri mitigates PD remain unclear. Here, we demonstrated that L. reuteri significantly alleviated MPTP-induced PD in mice. Importantly, we found that the protective effects of L. reuteri are mediated by its bioactive metabolites rather than the bacteria themselves. Specifically, L. reuteri elevated the levels of γ-aminobutyric acid (GABA). Administration of GABA to mice mitigated MPTP-induced PD. Mechanistically, GABA inhibited MPTP-induced ferroptosis in neuronal cells through activation of the AKT-GSK3β-GPX4 pathway via the GABA receptor. Collectively, our research elucidates that L. reuteri-derived GABA attenuates MPTP-induced PD by inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis, providing a potential therapeutic approach for the prevention and treatment of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"331 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218878","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

Association between functional gastrointestinal disorders and Parkinson’s disease in a prospective cohort study 一项前瞻性队列研究中功能性胃肠疾病与帕金森病的关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-04 DOI: 10.1038/s41531-025-01000-4

Yixiang Lin, Haoling Xu, Jiayi Zheng, Tianxin Lin, Minhui Wang, Tingting Huang, Fabin Lin, Qinyong Ye, Guoen Cai

引用次数: 0

Lower prevalence of metabolic syndrome and its components in the prediagnostic phase of Parkinson’s disease 帕金森病诊断前阶段代谢综合征及其组成部分患病率较低

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-04 DOI: 10.1038/s41531-025-01003-1

Hila Avisar, Uri Greenbaum, Ruth Djaldetti, Boaz Lerner

{"title":"Lower prevalence of metabolic syndrome and its components in the prediagnostic phase of Parkinson’s disease","authors":"Hila Avisar, Uri Greenbaum, Ruth Djaldetti, Boaz Lerner","doi":"10.1038/s41531-025-01003-1","DOIUrl":"https://doi.org/10.1038/s41531-025-01003-1","url":null,"abstract":"Investigating the association between metabolic syndrome (MetS) and all its components with prediagnostic Parkinson’s disease (PD) may clarify PD pathogenesis and identify candidates for prevention strategies and neuroprotective trials. We conducted a retrospective study of 890 PD patients diagnosed during 2000-2020 and 8,100 matched controls, analyzing electronic health records up to 15 years before PD diagnosis. Prevalence was assessed annually to track changes in association strength over time. PD patients consistently showed lower MetS prevalence (OR = 0.57–0.8). Compared to controls, PD patients had lower triglycerides (OR = 0.44–0.75), BMI (OR = 0.54–0.65), and hyperglycemia (OR = 0.81–0.86) rates, and females showed higher high-density lipoprotein (HDL) (OR = 1.48–1.82), lower low-density lipoprotein/HDL ratio (OR = 0.46–0.64), and reduced hypertension (OR = 0.79–0.85). These findings suggest an inverse association between MetS and PD years before diagnosis. We propose a lipid–blood pressure index incorporating triglycerides, HDL, and hypertension as a potential clinical tool for PD risk stratification.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"51 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211264","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

Proinflammatory and GABA eating bacteria in Parkinson's disease gut microbiome from a meta-analysis prospective 帕金森氏病肠道微生物群中的促炎菌和GABA食菌的荟萃分析前景

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-03 DOI: 10.1038/s41531-025-00950-z

Nour H. Marzouk, Hannah H. Rashwan, Mohamed El-Hadidi, Raghda Ramadan, Mohamed Mysara

{"title":"Proinflammatory and GABA eating bacteria in Parkinson's disease gut microbiome from a meta-analysis prospective","authors":"Nour H. Marzouk, Hannah H. Rashwan, Mohamed El-Hadidi, Raghda Ramadan, Mohamed Mysara","doi":"10.1038/s41531-025-00950-z","DOIUrl":"https://doi.org/10.1038/s41531-025-00950-z","url":null,"abstract":"Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by motor dysfunction coupled with gastrointestinal disturbances. Recent studies implicate the gut microbiome with the development of PD, yet pinpointing the exact microbial players is still to be determined. This meta-analysis is the first to consolidate five homogenous case-control studies, covering the same variable regions of the 16S rRNA of 1007 fecal samples. Utilizing our unified pipeline, we identified several key players potentially contributing to PD. Our findings reveal higher microbial diversity characterized by elevated levels GABA consuming species particularly Evtepia gabavorous, contributing to neuronal excitability. We also report the abundance of the proinflammatory Klebsiella variicola and the H2S-producing Streptococcus anginosus bacteria, potentially promoting α-synuclein accumulation in the brain. This comprehensive analysis highlights the potential of gut microbiota as a biomarker and a therapeutic strategy to mitigate the progression of PD, possibly facilitating diagnosis and enhancing patient outcomes.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211505","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

Resilience of striatal synaptic plasticity over early structural adaptations in premotor parkinsonism 运动前帕金森病纹状体突触可塑性在早期结构适应中的恢复力

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-03 DOI: 10.1038/s41531-025-00994-1

Leyre Merino-Galán, Marta Zamarbide, Arantzazu Belloso-Iguerategui, Marta C. Alonso-Moreno, Belén Gago, Alejandro Reinares-Sebastián, Javier Blesa, Dani Dumitriu, Ana Quiroga-Varela, María Cruz Rodríguez-Oroz

{"title":"Resilience of striatal synaptic plasticity over early structural adaptations in premotor parkinsonism","authors":"Leyre Merino-Galán, Marta Zamarbide, Arantzazu Belloso-Iguerategui, Marta C. Alonso-Moreno, Belén Gago, Alejandro Reinares-Sebastián, Javier Blesa, Dani Dumitriu, Ana Quiroga-Varela, María Cruz Rodríguez-Oroz","doi":"10.1038/s41531-025-00994-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00994-1","url":null,"abstract":"Parkinson’s disease has a long premotor phase with ongoing dopaminergic degeneration, yet its compensatory mechanisms remain unclear. Using a rat model with A53T α-synuclein overexpression in the substantia nigra, we analyzed striatal synaptic changes at 72 h, 1, 2, and 4 weeks post-inoculation, before motor signs appeared. Dopamine concentration decreased from 72 h, and chemical long-term potentiation was simultaneously inhibited, partially recovering by 4 weeks. At this time point, dopaminergic degeneration and post-synaptic morphological and ultrastructural dendritic spine remodelling became significant. These changes included a reduction in thin dendritic spines, an increase in mushroom spine head volume, a decrease in smooth endoplasmic reticulum-containing spines, and an increase in dendritic branching. In conclusion, impaired striatal dopaminergic neurotransmisson diminishes striatal synaptic plasticity, which can be partially restored through complex structural changes in striatal spines. These adaptations might represent fundamental homeostatic mechanisms regulating synaptic function during the premotor stage of Parkinson’s disease.<figure></figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"9 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211268","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

Prediction of all-cause mortality in Parkinson’s disease with explainable artificial intelligence using administrative healthcare data 利用行政医疗数据用可解释的人工智能预测帕金森病的全因死亡率

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-02 DOI: 10.1038/s41531-025-01007-x

You Hyun Park, Yong Wook Kim, Dae Ryong Kang, Sang Chul Lee, Seo Yeon Yoon

{"title":"Prediction of all-cause mortality in Parkinson’s disease with explainable artificial intelligence using administrative healthcare data","authors":"You Hyun Park, Yong Wook Kim, Dae Ryong Kang, Sang Chul Lee, Seo Yeon Yoon","doi":"10.1038/s41531-025-01007-x","DOIUrl":"https://doi.org/10.1038/s41531-025-01007-x","url":null,"abstract":"Many studies have reported increased mortality risk in patients with Parkinson’s disease (PD), but few have investigated the risk factors for PD mortality, including medical and socioeconomic factors. We applied an explainable artificial intelligence (XAI) model to predict long-term all-cause mortality in patients with PD using administrative healthcare data collected at PD diagnosis. Among seven machine learning algorithms, XGBoost achieved the best performance (10-year area under the receiver operating characteristic curve (AUROC): 0.836; 5-year AUROC: 0.894). The most important contributing feature to PD mortality was age, followed by male sex and pneumonia. Using XAI models, the nonlinear association between contributing factors and PD mortality was assessed, and an optimal target value to reduce mortality was found. In addition, prediction of individualized 10-year mortality risk for each PD participant was possible. Our XAI modeling pipeline demonstrated the feasibility to predict long-term mortality in patients with PD using preexisting healthcare data.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"81 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201944","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

Central biogenic amine deficiency with concomitant exploratory behavioral deficits in Dnajc12 knock-out mice Dnajc12基因敲除小鼠中枢生物胺缺乏伴探索性行为缺陷

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-30 DOI: 10.1038/s41531-025-00991-4

Isaac Bul Deng, Jordan Follett, Jesse D. Fox, Shannon Wall, Matthew J. Farrer

{"title":"Central biogenic amine deficiency with concomitant exploratory behavioral deficits in Dnajc12 knock-out mice","authors":"Isaac Bul Deng, Jordan Follett, Jesse D. Fox, Shannon Wall, Matthew J. Farrer","doi":"10.1038/s41531-025-00991-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00991-4","url":null,"abstract":"Bi-allelic autosomal recessive pathogenic variants in DNAJC12 lead to a constellation of neurological features, including young-onset Parkinson’s disease. DNAJC12 is a co-chaperone for enzymes involved in biogenic amines synthesis. In vitro, we discovered overexpressed DNAJC12 forms a complex with guanine triphosphate cyclohydrolase 1 (GCH1), a rate-limiting enzyme in the synthesis of tetrahydrobiopterin, a cofactor for biogenic amine synthesis. We also confirm DNAJC12’s interaction with tyrosine (TH) and tryptophan hydroxylases, paramount for dopamine (DA) and serotonin (5-HT) synthesis. In-vitro knock-down of DNAJC12 with a siRNA destabilizes DNAJC12-TH-GCH1 complex, whereas reciprocal co-overexpression of TH and GCH1 increases endogenous DNAJC12. Dnajc12 knock-out mice (DKO) exhibit reduced exploratory behavior at 3 months of age in open-field testing. In striatal tissue, total DA and 5-HT, and electrically evoked DA release are all reduced, with enhanced phosphorylation of Th at Ser31 and Ser40. DKO mice present models to develop/refine therapeutics approaches for biogenic amines disorders.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183747","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