NPJ Parkinson's Disease最新文献_第4页

LRRK2 rare-variant per-domain genetic burden in Parkinson’s Disease: association confined to the kinase domain 帕金森病的LRRK2罕见变异单结构域遗传负担：局限于激酶结构域的关联

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-29 DOI: 10.1038/s41531-025-00934-z

Sitki Cem Parlar, Konstantin Senkevich, Eric Yu, Jennifer A. Ruskey, Jamil Ahmad, Farnaz Asayesh, Dan Spiegelman, Cheryl Waters, Oury Monchi, Yves Dauvilliers, Nicolas Dupré, Lior Greenbaum, Sharon Hassin-Baer, Irina Miliukhina, Alla Timofeeva, Anton Emelyanov, Sofya Pchelina, Roy N. Alcalay, Edward A. Fon, Jean-François Trempe, Ziv Gan-Or

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Investigating plasma lipid profiles in association with Parkinson’s disease risk 研究血浆脂质谱与帕金森病风险的关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-28 DOI: 10.1038/s41531-025-00955-8

Houwen Zhang, Fangzheng Cao, Jialin Yu, Yu Liang, You Wu

引用次数: 0

Head-to-head comparison of four cerebrospinal fluid and three plasma neurofilament light chain assays in Parkinsonism 帕金森病四种脑脊液和三种血浆神经丝轻链试验的对比分析

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-28 DOI: 10.1038/s41531-025-00951-y

Simone Baiardi, Marcello Rossi, Giulia Giannini, Angela Mammana, Barbara Polischi, Luisa Sambati, Andrea Mastrangelo, Franco Magliocchetti, Pietro Cortelli, Sabina Capellari, Giovanna Calandra Buonaura, Piero Parchi

{"title":"Head-to-head comparison of four cerebrospinal fluid and three plasma neurofilament light chain assays in Parkinsonism","authors":"Simone Baiardi, Marcello Rossi, Giulia Giannini, Angela Mammana, Barbara Polischi, Luisa Sambati, Andrea Mastrangelo, Franco Magliocchetti, Pietro Cortelli, Sabina Capellari, Giovanna Calandra Buonaura, Piero Parchi","doi":"10.1038/s41531-025-00951-y","DOIUrl":"https://doi.org/10.1038/s41531-025-00951-y","url":null,"abstract":"Neurofilament light chain protein (NfL) is a valuable biomarker for the differential diagnosis between Parkinson’s disease (PD) and atypical parkinsonian disorders (APD). Here, we compared the performance of four cerebrospinal fluid (CSF) and three plasma NfL immunoassays in 253 PD and 265 APD. We measured NfL by ELISA in CSF and by SiMoA, CLEIA, and ELLA in both CSF and plasma. Additionally, we assessed Lewy body pathology by CSF α-synuclein real-time quaking-induced conversion assay (α-syn-RT-QuIC). In each biofluid, the tested assays showed comparable precision; however, CSF NfL showed higher diagnostic accuracy than plasma NfL for discriminating PD from APD (AUC range 0.966–0.974 vs 0.917–0.924). Combining CSF NfL and α-syn-RT-QuIC increased diagnostic accuracy. These results confirm the high diagnostic value of NfL in patients with parkinsonism, even when different assays are used. Combining CSF NfL and α-syn-RT-QuIC provides the highest accuracy, followed by CSF NfL and plasma NfL.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880733","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

Prevalence of experienced changes in artistic and everyday creativity in people with Parkinson’s disease 帕金森氏症患者艺术和日常创造力变化的普遍性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-27 DOI: 10.1038/s41531-025-00924-1

Blanca T. M. Spee, Julia S. Crone, Sirwan K. L. Darweesh, Marjan J. Meinders, Jozsef Arato, Young Ah Kim, Bastiaan R. Bloem, Matthew Pelowski

{"title":"Prevalence of experienced changes in artistic and everyday creativity in people with Parkinson’s disease","authors":"Blanca T. M. Spee, Julia S. Crone, Sirwan K. L. Darweesh, Marjan J. Meinders, Jozsef Arato, Young Ah Kim, Bastiaan R. Bloem, Matthew Pelowski","doi":"10.1038/s41531-025-00924-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00924-1","url":null,"abstract":"Creativity is the ability to generate novel and meaningful ideas or behaviors, encompassing both artistic originality and personal satisfaction. Emerging evidence suggests that people with Parkinson’s disease (PD) may experience changes in creativity. This study examines the prevalence of creativity changes in PD using cross-sectional data from the Netherlands (PRIME-NL, 2021–2023). Participants (N = 793) self-reported creativity changes, demographics, clinical factors, and pre-diagnosis creative engagement via a self-structured questionnaire. Descriptive analyses revealed that 41% of respondents reported creativity changes: 12% experienced an increase, 22% a decrease, and 7% fluctuations. Ordinal regression analysis showed that longer disease duration and dopamine agonists were associated with increased creativity, while older age and prior creative engagement predicted decreases. A sub-cohort (n = 292) reported creativity changes across seven domains, with changes most frequently observed in everyday creativity, sports/movement, and fine art/design. These findings underscore the need for further research on creativity in PD to inform person-centered treatment strategies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877895","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 serum myeloperoxidase enzyme activity and Parkinson’s disease status 血清髓过氧化物酶活性与帕金森病状态的关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-26 DOI: 10.1038/s41531-025-00941-0

Emilio Fernández Espejo, María-del-Mar Guerra, Silvia Castellano

{"title":"Association between serum myeloperoxidase enzyme activity and Parkinson’s disease status","authors":"Emilio Fernández Espejo, María-del-Mar Guerra, Silvia Castellano","doi":"10.1038/s41531-025-00941-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00941-0","url":null,"abstract":"Elevated levels of the inflammatory enzyme myeloperoxidase (MPO) in the blood are associated with the development of age-related inflammatory diseases. Given that age, inflammation, and blood MPO play a role in the pathogenesis of Parkinson´s disease (PD), we hypothesized that serum MPO could be associated with PD status. This case-control study (199 participants) was conducted using an extensive protocol, and the concentration and activity of MPO in blood serum were measured. The findings reveal that serum MPO concentration and activity are significantly increased in the patients, and that rates of PD in all individuals are associated with increasing tertiles of MPO concentration and activity. In multivariate logistic regression model adjusting for confounding factors, MPO activity (not concentration) is the factor that is most associated with PD status (OR, 6.921, P = 0.001). Mental depression is directly associated with MPO activity and with PD status (OR, 0.121, B = −2.108, P = 0.002). The use of statins or nonsteroidal anti-inflammatory drugs significantly reduces serum MPO activity, but the possible association with the odds of having PD does not survive correction for multiple testing. In summary, both serum MPO concentration and activity are increased in patients with PD, but only MPO enzyme activity is associated with PD status. These findings may have implications for the evaluation of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875994","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 characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction 帕金森病的特征是维生素b6依赖性炎症性犬尿氨酸途径功能障碍

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-26 DOI: 10.1038/s41531-025-00964-7

Edward N. Wilson, Jacob Umans, Michelle S. Swarovski, Paras S. Minhas, Justin H. Mendiola, Øivind Midttun, Arve Ulvik, Marian Shahid-Besanti, Patricia Linortner, Siddhita D. Mhatre, Qian Wang, Divya Channappa, Nicole K. Corso, Lu Tian, Carolyn A. Fredericks, Geoffrey A. Kerchner, Edward D. Plowey, Brenna Cholerton, Per M. Ueland, Cyrus P. Zabetian, Nora E. Gray, Joseph F. Quinn, Thomas J. Montine, Sharon J. Sha, Frank M. Longo, David A. Wolk, Alice Chen-Plotkin, Victor W. Henderson, Tony Wyss-Coray, Anthony D. Wagner, Elizabeth C. Mormino, Nima Aghaeepour, Kathleen L. Poston, Katrin I. Andreasson

{"title":"Parkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction","authors":"Edward N. Wilson, Jacob Umans, Michelle S. Swarovski, Paras S. Minhas, Justin H. Mendiola, Øivind Midttun, Arve Ulvik, Marian Shahid-Besanti, Patricia Linortner, Siddhita D. Mhatre, Qian Wang, Divya Channappa, Nicole K. Corso, Lu Tian, Carolyn A. Fredericks, Geoffrey A. Kerchner, Edward D. Plowey, Brenna Cholerton, Per M. Ueland, Cyrus P. Zabetian, Nora E. Gray, Joseph F. Quinn, Thomas J. Montine, Sharon J. Sha, Frank M. Longo, David A. Wolk, Alice Chen-Plotkin, Victor W. Henderson, Tony Wyss-Coray, Anthony D. Wagner, Elizabeth C. Mormino, Nima Aghaeepour, Kathleen L. Poston, Katrin I. Andreasson","doi":"10.1038/s41531-025-00964-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00964-7","url":null,"abstract":"Recent studies demonstrate that Parkinson’s disease (PD) is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). Here, we used mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. We found increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B6 deficiency. Furthermore, increased QA tracked with CSF tau, CSF soluble TREM2 (sTREM2) and severity of both motor and non-motor PD clinical symptoms. Finally, PD patient subgroups with distinct KP profiles displayed distinct PD clinical features. These data validate the KP as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"5 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877898","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

Subthalamic stimulation evokes hyperdirect high beta interruption and cortical high gamma entrainment in Parkinson’s disease 在帕金森病中，丘脑下刺激引起超直接高β中断和皮质高γ携带

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-26 DOI: 10.1038/s41531-025-00965-6

Ádám József Berki, Hao Ding, Marcell Palotai, László Halász, Loránd Erőss, Gábor Fekete, László Bognár, Péter Barsi, Andrea Kelemen, Borbála Jávor-Duray, Éva Pichner, Muthuraman Muthuraman, Gertrúd Tamás

{"title":"Subthalamic stimulation evokes hyperdirect high beta interruption and cortical high gamma entrainment in Parkinson’s disease","authors":"Ádám József Berki, Hao Ding, Marcell Palotai, László Halász, Loránd Erőss, Gábor Fekete, László Bognár, Péter Barsi, Andrea Kelemen, Borbála Jávor-Duray, Éva Pichner, Muthuraman Muthuraman, Gertrúd Tamás","doi":"10.1038/s41531-025-00965-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00965-6","url":null,"abstract":"Compound network dynamics in beta and gamma bands determine the severity of bradykinesia in Parkinson’s disease. We explored its subthalamic stimulation related changes parallel with improvement of complex hand movements. Thirty eight patients with Parkinson’s disease treated with bilateral stimulation accomplished voluntary and traced spiral drawing with their more affected hand on a digital tablet. A 64 channel electroencephalography was recorded, low and high beta and gamma power was computed in subthalamic and motor cortical sources at four stimulation levels. Subthalamic cortical effective connectivity was calculated, and subnetwork models were created. Beta power decreased, and gamma power increased in sources ipsilateral to stimulation with increasing stimulation intensity. Networks comprising the primary motor cortex played a dominant role in predicting the improvement of voluntary drawing speed. Subthalamic stimulation diminished the hyperdirect high beta information processing and promoted the cortico cortical interactions of the primary motor cortex in the high gamma band.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"16 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877901","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

Four questions to predict cognitive decline in de novo Parkinson’s disease 预测新生帕金森病认知能力下降的四个问题

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-25 DOI: 10.1038/s41531-025-00958-5

Jan Hlavnička, Josef Mana, Ondrej Bezdicek, Martin Čihák, Filip Havlík, Dominik Škrabal, Tereza Bartošová, Karel Šonka, Evžen Růžička, Petr Dušek

{"title":"Four questions to predict cognitive decline in de novo Parkinson’s disease","authors":"Jan Hlavnička, Josef Mana, Ondrej Bezdicek, Martin Čihák, Filip Havlík, Dominik Škrabal, Tereza Bartošová, Karel Šonka, Evžen Růžička, Petr Dušek","doi":"10.1038/s41531-025-00958-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00958-5","url":null,"abstract":"Early identification of cognitive decline (CD) in de novo Parkinson’s disease (PD) is crucial for choosing appropriate therapies and recruiting for clinical trials. However, existing prognostic models lack flexibility, scalability and require costly instrumentation. This study explores the utility of standard clinical questionnaires and criteria to predict CD in de novo PD. A total of 186 patients from the Parkinson Progression Markers Initiative (PPMI) and 48 patients from the Biomarkers of Parkinson’s Disease project (BIO-PD) underwent clinical interviews, comprehensive tests, and questionnaires. A model based only on age of disease onset, history of stroke, history of fainting, and vocalization during dreams predicted CD in 2 and 4-year horizons with an area under curve (AUC) of 70% ± 10% standard deviation (cross-validated PPMI), 79% (overall PPMI), and 78% (validation in BIO-PD). This approach enables rapid preliminary screening using just four simple questions, achieving predictive accuracy comparable to instrumentation-based methods while reducing assessment time.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"37 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872651","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

IC100 blocks inflammasome activation induced by α-synuclein aggregates and ASC specks IC100阻断α-突触核蛋白聚集体和ASC斑点诱导的炎性小体活化

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-25 DOI: 10.1038/s41531-025-00963-8

Brianna Cyr, Regina T. Vontell, Roey Hadad, Juan Pablo de Rivero Vaccari, Robert W. Keane

{"title":"IC100 blocks inflammasome activation induced by α-synuclein aggregates and ASC specks","authors":"Brianna Cyr, Regina T. Vontell, Roey Hadad, Juan Pablo de Rivero Vaccari, Robert W. Keane","doi":"10.1038/s41531-025-00963-8","DOIUrl":"https://doi.org/10.1038/s41531-025-00963-8","url":null,"abstract":"Parkinson’s disease (PD) is associated with chronic sterile inflammation and persistent inflammasome activation involving α-synuclein and ASC protein aggregates, but the underlying mechanisms of the neuroinflammatory response remain unclear. Here, we used midbrain postmortem samples from donors with and without α-synucleinopathies to assess the expression of inflammasome proteins in patients with Parkinsonism. We show that dopaminergic neurons exhibit increased expression of ASC, NOD-like receptor protein (NLRP) 1, and modification of α-synuclein phosphorylation at serine129 (pS129) within the Lewy body inclusions, whereas NLRP3 was identified mainly in microglial. Moreover, treatment of LRRK2 cells with ASC specks from PD and Lewy body dementia patients induced inflammasome activation and cytotoxicity that was blocked by IC100. Administration of preformed α-synuclein aggregates to microglia resulted in a significant elevation in pS129, and this effect was also blocked by IC100. Thus, IC100 may be a promising therapeutic strategy for inflammatory disease modification in synucleinopathies and other diseases.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"74 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872652","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 brain degeneration patterns in early-stage Parkinson’s disease: a multimodal MRI study 识别早期帕金森病的脑退化模式：一项多模态MRI研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-25 DOI: 10.1038/s41531-025-00975-4

Zihao Zhu, Jiaqi Wen, Xiaojie Duanmu, Weijin Yuan, Qianshi Zheng, Tao Guo, Chenqing Wu, Haoting Wu, Cheng Zhou, Qingze Zeng, Jianmei Qin, Jingjing Wu, Jingwen Chen, Yuelin Fang, Bingting Zhu, Yaping Yan, Jun Tian, Baorong Zhang, Minming Zhang, Xiaojun Guan, Xiaojun Xu

{"title":"Identifying brain degeneration patterns in early-stage Parkinson’s disease: a multimodal MRI study","authors":"Zihao Zhu, Jiaqi Wen, Xiaojie Duanmu, Weijin Yuan, Qianshi Zheng, Tao Guo, Chenqing Wu, Haoting Wu, Cheng Zhou, Qingze Zeng, Jianmei Qin, Jingjing Wu, Jingwen Chen, Yuelin Fang, Bingting Zhu, Yaping Yan, Jun Tian, Baorong Zhang, Minming Zhang, Xiaojun Guan, Xiaojun Xu","doi":"10.1038/s41531-025-00975-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00975-4","url":null,"abstract":"Parkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder. This study aimed to identify different patterns of early brain degeneration in PD patients and investigate their clinical relevance. 179 early-stage PD patients and 115 healthy controls were included. We assessed cortical morphology, white matter microstructure, and subcortical iron metabolism using multimodal magnetic resonance imaging and employed clustering techniques to identify subtypes. Two subtypes were identified: the early-deterioration subtype, characterized by fronto-temporal atrophy, parietal thickening, widespread reductions in fractional anisotropy (FA) values, and increased subcortical iron content, which exhibited more severe baseline symptoms and a trend of faster memory decline; and the early-compensatory subtype, characterized by rostral middle frontal atrophy, parietal-occipital thickening, increased FA values, and normal iron content, which exhibited milder symptoms initially but experienced faster progression of both motor and non-motor symptoms. These discoveries provided new insights into disease heterogeneity and facilitated the exploration of early neurodegenerative mechanisms.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"4 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876094","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