NPJ Parkinson's Disease最新文献

Application of new biologic disease criteria for synucleinopathies to the systemic synuclein sampling study cohort

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-06 DOI: 10.1038/s41531-025-00919-y

L. M. Chahine, M. C. Brumm, A. R. Nair, S. Mosovsky, N. K. Polinski, T. G. Beach, B. Mollenhauer, C. H. Adler

引用次数: 0

Non-invasive brain stimulation to modulate neural activity in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-05 DOI: 10.1038/s41531-025-00908-1

Manuel Bange, Rick C. G. Helmich, Aparna A. Wagle Shukla, Günther Deuschl, Muthuraman Muthuraman

引用次数: 0

A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-04 DOI: 10.1038/s41531-025-00885-5

Janis Rebecca Bedarf, Stefano Romano, Silke Sophie Heinzmann, Anthony Duncan, Maria H. Traka, Duncan Ng, Daniella Segovia-Lizano, Marie-Christine Simon, Arjan Narbad, Ullrich Wüllner, Falk Hildebrand

{"title":"A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease","authors":"Janis Rebecca Bedarf, Stefano Romano, Silke Sophie Heinzmann, Anthony Duncan, Maria H. Traka, Duncan Ng, Daniella Segovia-Lizano, Marie-Christine Simon, Arjan Narbad, Ullrich Wüllner, Falk Hildebrand","doi":"10.1038/s41531-025-00885-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00885-5","url":null,"abstract":"Current treatment of Parkinson’s Disease (PD) remains symptomatic, and disease-modifying approaches are urgently required. A promising approach is to modify intestinal microbiota and key metabolites of bacterial fermentation: short-chain fatty acids (SCFA), which are decreased in PD. A prospective, controlled pilot study (DRKS00034528) was conducted on 11 couples (PD patient plus healthy spouse as control (CO)). Participants followed a 4-week diet rich in dietary fibre, including intake of the prebiotic Lactulose. Gut metagenomes, faecal and urinary metabolites, and clinical characteristics were assessed. The dietary intervention significantly augmented faecal SCFA and increased Bifidobacteria spp., reducing PD-related gastrointestinal symptoms. The pre-existing bacterial dysbiosis in PD (depletion of Blautia, Dorea, Erysipelatoclostridium) persisted. Bacterial metabolite composition in faeces and urine positively changed with the intervention: Brain-relevant gut metabolic functions involved in neuroprotective and antioxidant pathways, including S-adenosyl methionine, glutathione, and inositol, improved in PD. These promising results warrant further investigation in larger cohorts.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"183 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775629","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

Hyposmia in Parkinson’s disease; exploring selective odour loss 帕金森病的嗅觉减退；探索选择性气味丧失

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-04 DOI: 10.1038/s41531-025-00922-3

Eleanor Mitchell, Christian Mattjie, Jonathan P. Bestwick, Rodrigo C. Barros, Artur F. Schuh, Cristina Simonet, Alastair J. Noyce

{"title":"Hyposmia in Parkinson’s disease; exploring selective odour loss","authors":"Eleanor Mitchell, Christian Mattjie, Jonathan P. Bestwick, Rodrigo C. Barros, Artur F. Schuh, Cristina Simonet, Alastair J. Noyce","doi":"10.1038/s41531-025-00922-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00922-3","url":null,"abstract":"Smell loss is a frequent and early manifestation of Parkinson’s disease (PD), serving as a sensitive - albeit nonspecific - clinical biomarker1. The notion that PD causes odour-selective hyposmia has been debated for three decades. Previous studies have used healthy controls as the comparator; this is problematic given the majority presumably display normal olfactory function. Using University of Pennsylvania Smell Identification Test data from the Parkinson’s Progression Markers Initiative, we trained eight machine learning models to distinguish ‘PD hyposmia’ (n = 155) from ‘non-PD hyposmia’ (n = 155). The best-performing models were evaluated on an independent validation cohort. While specific responses (e.g. mistaking pizza for bubble gum) were impactful across models, at best only 63% of PD cases were correctly identified. Given we used a balanced data set, 50% accuracy would be achieved by random guessing. This suggests that PD-related hyposmia does not exhibit a unique pattern of odour selectivity distinct from general hyposmia.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"39 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782536","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

Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease 早期帕金森病有意义症状和功能影响的系统回顾和共识概念模型

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-03 DOI: 10.1038/s41531-025-00907-2

Jennifer R. Mammen, Jamie L. Adams, Rikki Mangrum, Yuge Xiao, William Barbosa, Mirinda Tyo, Christopher Redmond, Cheryl Carter, Kelly Cifelli, Robert Cifelli, Hope Maruzo, Jim Meeker, Gerry Shultz, Colbren Thomas, Claire Bale, Evan Davies, Catherine M. Kopil, Connie Marras, Tiago Mestre, Thomas Morel, Tanya Simuni, Glenn T. Stebbins, Daniel Weintraub, Diane Stephenson

{"title":"Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease","authors":"Jennifer R. Mammen, Jamie L. Adams, Rikki Mangrum, Yuge Xiao, William Barbosa, Mirinda Tyo, Christopher Redmond, Cheryl Carter, Kelly Cifelli, Robert Cifelli, Hope Maruzo, Jim Meeker, Gerry Shultz, Colbren Thomas, Claire Bale, Evan Davies, Catherine M. Kopil, Connie Marras, Tiago Mestre, Thomas Morel, Tanya Simuni, Glenn T. Stebbins, Daniel Weintraub, Diane Stephenson","doi":"10.1038/s41531-025-00907-2","DOIUrl":"https://doi.org/10.1038/s41531-025-00907-2","url":null,"abstract":"A comprehensive, patient-centered conceptual model of early Parkinson’s is lacking and is greatly needed. A systematic review and meta-synthesis of qualitative and quantitative research was conducted by a multi-stakeholder taskforce using JBI Mixed Methods Review criteria and GRADE-CERQual standards for assessment of evidence. Over 340 symptoms and impacts were identified across ten symptom domains (Movement, Cognitive, Psychiatric, Sleep, Sensory, Speech, Digestive, Urinary, Sexual, Autonomic) and two impact domains (Physical and Psychosocial functioning). A wide range of motor and non-motor symptoms were present in early disease, with strongest support for tremor, dexterity, gait, stiffness, slow movements, cognitive, mood, and sleep alterations, urinary dysfunction, constipation, pain, and fatigue. These affected mobility, self-concept, coping, effort of living, interactions and important activities, with evidence of many understudied concepts. This model offers the most comprehensive catalogue of symptoms and impacts in Parkinson’s to date and will support clinical practice and endpoint selection for therapeutic trials.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"107 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766626","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

Predictive modeling to uncover Parkinson’s disease characteristics that delay diagnosis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-02 DOI: 10.1038/s41531-025-00923-2

Tom Hähnel, Tamara Raschka, Jochen Klucken, Enrico Glaab, Jean-Christophe Corvol, Björn H. Falkenburger, Holger Fröhlich

引用次数: 0

Deciphering shared molecular dysregulation across Parkinson’s disease variants using a multi-modal network-based data integration and analysis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-31 DOI: 10.1038/s41531-025-00914-3

Alise Zagare, Irina Balaur, Adrien Rougny, Claudia Saraiva, Matthieu Gobin, Anna S. Monzel, Soumyabrata Ghosh, Venkata P. Satagopam, Jens C. Schwamborn

{"title":"Deciphering shared molecular dysregulation across Parkinson’s disease variants using a multi-modal network-based data integration and analysis","authors":"Alise Zagare, Irina Balaur, Adrien Rougny, Claudia Saraiva, Matthieu Gobin, Anna S. Monzel, Soumyabrata Ghosh, Venkata P. Satagopam, Jens C. Schwamborn","doi":"10.1038/s41531-025-00914-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00914-3","url":null,"abstract":"Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no effective treatment. Advances in neuroscience and systems biomedicine now enable the use of complex patient-specific in vitro disease models and cutting-edge computational tools for data integration, enhancing our understanding of complex PD mechanisms. To explore common biomedical features across monogenic PD forms, we developed a knowledge graph (KG) by integrating previously published high-content imaging and RNA sequencing data of PD patient-specific midbrain organoids harbouring LRRK2-G2019S, SNCA triplication, GBA-N370S or MIRO1-R272Q mutations with publicly available biological data. Furthermore, we generated a single-cell RNA sequencing dataset of midbrain organoids derived from idiopathic PD patients (IPD) to stratify IPD patients within the spectrum of monogenic forms of PD. Despite the high degree of PD heterogeneity, we found that common transcriptomic dysregulation in monogenic PD forms is reflected in glial cells of IPD patient midbrain organoids. In addition, dysregulation in ROBO signalling might be involved in shared pathophysiology between monogenic PD and IPD cases.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745575","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 homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-28 DOI: 10.1038/s41531-025-00905-4

Lin-Hua Gan, Yi-Min Sun, Xin-Yue Zhou, Zhi-Yuan Qi, Feng-Tao Liu, Yi-Lin Tang, Wen-bo Yu, Bao-Guo Xiao, Jian Wang, Jian-Jun Wu

{"title":"The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism","authors":"Lin-Hua Gan, Yi-Min Sun, Xin-Yue Zhou, Zhi-Yuan Qi, Feng-Tao Liu, Yi-Lin Tang, Wen-bo Yu, Bao-Guo Xiao, Jian Wang, Jian-Jun Wu","doi":"10.1038/s41531-025-00905-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00905-4","url":null,"abstract":"The leucine-rich repeat kinase 2 (LRRK2) gene is one of the most common genetic causes of autosomal dominant Parkinson’s disease (PD) and a common genetic risk factor for sporadic PD. However, aged mice with common LRRK2 point mutations fail to exhibit age-related PD-associated behavioral and pathological impairments. We generated a novel mouse model harboring the LRRK2.p.N1437D point mutation (c.4309 A > G; NM_98578). Here, the homozygous N1437D mutation, but not the heterozygous mutation, led to an increase in the autophosphorylation, substrate phosphorylation, and GTP-binding capacity of LRRK2. Heterozygous N1437D mice also showed unaffected behavior and pathology while the homozygous mice exhibited PD-associated behavioral change at 25–26 months, dopamine system damage, lipofuscin accumulation, and lipid peroxidation in substantia nigra dopaminergic neurons at 26–27 months. The new N1437D point mutation mouse does not require LRRK2 overexpression and may better mimic the pathological characteristics of LRRK2 mutation in the ROC-COR region.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"63 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723449","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 of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-28 DOI: 10.1038/s41531-025-00909-0

Ruolan Lin, Guoen Cai, Ying Chen, Jinmei Zheng, Shu Wang, Huinan Xiao, Qinyong Ye, Yunjing Xue, Rifeng Jiang

{"title":"Association of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson’s disease","authors":"Ruolan Lin, Guoen Cai, Ying Chen, Jinmei Zheng, Shu Wang, Huinan Xiao, Qinyong Ye, Yunjing Xue, Rifeng Jiang","doi":"10.1038/s41531-025-00909-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00909-0","url":null,"abstract":"Growing evidence highlights the roles of glymphatic system and peripheral inflammation in Parkinson’s disease (PD). We evaluated their interrelationship and potential mechanisms contributing to motor symptoms using DTI-ALPS and inflammatory markers (leukocyte, lymphocyte, neutrophil counts, neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) in 134 PD patients (52 tremor-dominant [TD], 62 postural instability and gait difficulty [PIGD]) and 81 healthy controls (HC, 33 with inflammatory markers). PD exhibited lower DTI-ALPS than HC (1.43 ± 0.19 vs. 1.52 ± 0.21, p = 0.001). DTI-ALPS was negatively correlated with NLR, PLR, and neutrophils in PD (all p < 0.05) and with neutrophils in PIGD (β = –0.043, p = 0.048), and positively correlated with lymphocytes in TD (β = 0.105, p = 0.034). DTI-ALPS mediated the relationship between peripheral inflammation (NLR and neutrophils) and MDS-UPDRS III score in PD. Overall, glymphatic dysfunction correlates with peripheral inflammation and may mediate effects of inflammation on motor symptoms in PD, with distinct inflammation profiles between TD and PIGD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"100 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734063","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

Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-27 DOI: 10.1038/s41531-025-00917-0

Fatema Currim, Josephine Brown-Leung, Tauqeerunnisa Syeda, Matthew Corson, Sofia Schumann, Wenzhu Qi, Priyanka Baloni, Jonathan H. Shannahan, Jean-Christophe Rochet, Rajesh Singh, Jason R. Cannon

{"title":"Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death","authors":"Fatema Currim, Josephine Brown-Leung, Tauqeerunnisa Syeda, Matthew Corson, Sofia Schumann, Wenzhu Qi, Priyanka Baloni, Jonathan H. Shannahan, Jean-Christophe Rochet, Rajesh Singh, Jason R. Cannon","doi":"10.1038/s41531-025-00917-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00917-0","url":null,"abstract":"How extracellular vesicles (EVs) may contribute to mechanisms of primary intracellular pathogenesis in Parkinson’s disease (PD) remains unknown. To critically advance our understanding of how EVs influence early-stage PD pathogenesis, we tested the hypothesis that rats acutely exposed to the PD neurotoxin rotenone would produce differential miRNAs in CSF/serum-derived EVs and that such modulation would be responsible for PD-relevant functional alterations in recipient neuronal cells. We discovered that acute rotenone treatment produced significant and specific serum miRNA alterations. Primary midbrain neurons treated with serum EVs from rotenone-exposed rats produced oxidative stress, mitochondrial toxicity, and cell loss in neuronal culture. These mechanisms were dependent on miR-30a-5p and miR-484. Thus, this study has elucidated that differential expression of miRNAs in circulating EVs from serum/CSF of rats is a potential early diagnostic marker for PD, and that the modulation of cellular functions and viability due to extracellular vesicles determines the pathological fate.<figure></figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"125 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712735","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