NPJ Parkinson's Disease最新文献_第4页

Predicting cognition after subthalamic Deep Brain Stimulation in Parkinson’s Disease 预测帕金森病丘脑下深部脑刺激后的认知

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-28 DOI: 10.1038/s41531-025-01128-3

Dorothee Kübler-Weller, Heiner Stuke, Melanie Astalosch, Luísa Martins Ribeiro, Elias Landfried, Gerd-Helge Schneider, Katharina Faust, Patricia Krause, Jan Roediger, Stefan Haufe, Mahta Mousavi, Bassam Al-Fatly, Claudia Spies, Friedrich Borchers, Andrea A. Kühn

{"title":"Predicting cognition after subthalamic Deep Brain Stimulation in Parkinson’s Disease","authors":"Dorothee Kübler-Weller, Heiner Stuke, Melanie Astalosch, Luísa Martins Ribeiro, Elias Landfried, Gerd-Helge Schneider, Katharina Faust, Patricia Krause, Jan Roediger, Stefan Haufe, Mahta Mousavi, Bassam Al-Fatly, Claudia Spies, Friedrich Borchers, Andrea A. Kühn","doi":"10.1038/s41531-025-01128-3","DOIUrl":"https://doi.org/10.1038/s41531-025-01128-3","url":null,"abstract":"Cognitive deficits have a high impact on quality of life in Parkinson’s disease (PD). This study takes into account the multifaceted etiology of cognition to estimate the cognitive outcome after deep brain stimulation (DBS) surgery in PD. Clinical, neuropsychological, perioperative, neuroimaging- and laboratory-based risk factors for cognitive dysfunction were prospectively assessed prior to surgery in 57 patients (21 female; age 60.2 ± 8.2; disease duration 10.5 ± 5.9 years, preregistered 9 June 2019 at clinicaltrials.gov, NCT03982953). Elastic net regularized regression and leave-one-out cross-validation were used to fit a multivariable model with the Montréal Cognitive Assessment (MoCA) change one year after surgery as primary outcome. The backward span had the most robust association with the cognitive outcome (rho = 0.499, p < 0.001**; c = 0.302). We propose a post-hoc prediction model for cognition based on the baseline MoCA and backward span (R² = 0.50). After clinical validation, our short and easily applicable prediction model could improve informed therapeutic decision making.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915367","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

Longitudinal non-negative matrix factorization identifies the altered trajectory of motor symptoms in Parkinson’s disease 纵向非负矩阵分解识别帕金森病运动症状的改变轨迹

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-28 DOI: 10.1038/s41531-025-01127-4

Xinmin Hou, Kai Zhou, Yuxuan Wu, Rong Li, Jiali Yu, Qin Chen, Fengmei Lu, Huafu Chen, Qing Gao

{"title":"Longitudinal non-negative matrix factorization identifies the altered trajectory of motor symptoms in Parkinson’s disease","authors":"Xinmin Hou, Kai Zhou, Yuxuan Wu, Rong Li, Jiali Yu, Qin Chen, Fengmei Lu, Huafu Chen, Qing Gao","doi":"10.1038/s41531-025-01127-4","DOIUrl":"https://doi.org/10.1038/s41531-025-01127-4","url":null,"abstract":"Parkinson’s disease (PD) is the second most common neurodegenerative disease with progressive structural alterations throughout the brain, resulting in motor symptoms that seriously affect patients’ daily life. The present study then aimed to explore the progressive co-changes in gray matter patterns in PD and identify the longitudinal neuroimaging biomarkers that could predict the progressive motor symptoms of PD. Non-negative Matrix Factorization (NMF) was first used to decompose gray matter images into 7 latent factors from healthy samples, and then the latent factors were validated on an independent dataset to verify the stability of the structural factors. Parkinson’s patients (including baseline, 1-year follow-up, and 2-year follow-up data) and healthy controls (HC) from Parkinson’s Progression Markers Initiative (PPMI) were used to find the correlation between factor weights and motor-symptom related Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores. The decreasing trend of the factor weights with increasing disease duration was found in the first 6 factors. The XGBoost prediction model demonstrated that Factor 2 (motor function), 3 (perceptual processing) & 7 (cerebellum) played pivotal roles in longitudinally predicting MDS-UPDRS-Ⅱ scores, whereas Factor 3 & 5 (subcortical basal ganglia) accounted for most change in MDS-UPDRS-Ⅲ. Our research indicated that the NMF factors could capture the progressive alterations of structural architectures in PD, and the factor weights were capable of predicting the clinical motor symptoms. This provides new perspectives for exploring the neural mechanisms underlying the disease and future clinical diagnostic and therapeutic approaches associated with disease progression.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"56 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910956","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

Balancing practicality and complexity in neuroimaging models of Parkinson’s disease progression 平衡帕金森病进展的神经成像模型的实用性和复杂性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-27 DOI: 10.1038/s41531-025-01125-6

Valtteri Kaasinen, Thilo van Eimeren

引用次数: 0

Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation c端截断在α -突触核蛋白病理和路易体形成中的差异作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-26 DOI: 10.1038/s41531-025-01084-y

Anne-Laure Mahul-Mellier, Melek Firat Altay, Niran Maharjan, Nadine Ait-Bouziad, Anass Chiki, Somanath Jagannath, Galina Limorenko, Salvatore Novello, Jonathan Ricci, Yllza Jasiqi, Siv Vingill, Richard Wade-Martins, Janice Holton, Catherine Strand, Caroline Haikal, Jia-Yi Li, Romain Hamelin, Marie Croisier, Graham Knott, Georges Mairet-Coello, Laura Weerens, Anne Michel, Patrick Downey, Martin Citron, Hilal A. Lashuel

{"title":"Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation","authors":"Anne-Laure Mahul-Mellier, Melek Firat Altay, Niran Maharjan, Nadine Ait-Bouziad, Anass Chiki, Somanath Jagannath, Galina Limorenko, Salvatore Novello, Jonathan Ricci, Yllza Jasiqi, Siv Vingill, Richard Wade-Martins, Janice Holton, Catherine Strand, Caroline Haikal, Jia-Yi Li, Romain Hamelin, Marie Croisier, Graham Knott, Georges Mairet-Coello, Laura Weerens, Anne Michel, Patrick Downey, Martin Citron, Hilal A. Lashuel","doi":"10.1038/s41531-025-01084-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01084-y","url":null,"abstract":"Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson’s disease and synucleinopathies. However, the precise role of these PTM in pathology formation, neurodegeneration, and pathology spreading remains unclear. Here, we systematically investigated the role of post-fibrillization C-terminal aSyn truncations in regulating uptake, processing, seeding, and LB-like inclusion formation using a neuronal seeding model that recapitulates LB formation and neurodegeneration. We show that C-terminal cleavage of aSyn fibrils occurs rapidly post exogenous fibril internalization and during intracellular LB-like inclusion formation. Blocking cleavage of internalized fibrils does not affect seeding, but inhibiting enzymes such as calpains 1 and 2 alters LB-like inclusion formation. We show that C-terminal truncations, along with other PTMs, regulate fibril interactome remodeling, shortening, lateral association, and packing. These findings reveal distinct roles of C-terminal truncations at different aggregation stages on the pathway to LB formation, highlighting the need for consideration of stage‑specific strategies to target aSyn proteolytic cleavages.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"51 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899291","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

Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson’s disease 新的原位播种免疫检测方法揭示了帕金森病中神经元驱动的α -突触核蛋白播种

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-25 DOI: 10.1038/s41531-025-01111-y

Maria Otero-Jimenez, Marcelina J. Wojewska, Simona Jogaudaite, David Miller, Sandra Gray-Rodriguez, Grainne C. Geoghegan, Laura Abelleira-Hervas, Tim James Viney, Barbara Sarkany, Djordje Gveric, Steve Gentleman, Javier Alegre-Abarrategui

{"title":"Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson’s disease","authors":"Maria Otero-Jimenez, Marcelina J. Wojewska, Simona Jogaudaite, David Miller, Sandra Gray-Rodriguez, Grainne C. Geoghegan, Laura Abelleira-Hervas, Tim James Viney, Barbara Sarkany, Djordje Gveric, Steve Gentleman, Javier Alegre-Abarrategui","doi":"10.1038/s41531-025-01111-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01111-y","url":null,"abstract":"Aggregates of alpha-synuclein (α-syn) propagate through template-induced misfolding in people with Parkinson’s disease (PD) and Multiple System Atrophy (MSA). Prion-like seeding is crucial in disease initiation and progression, representing a major target for disease-modifying therapies. The detection of α-syn seeding with seeding amplification assays (SAAs) has remarkable diagnostic and research potential. However, current SAAs rely on bulk tissue homogenates or fluids, losing critical spatial and cellular resolution. Here, we report our novel in situ seeding immunodetection (isSID) assay that enables the visualization of seeding with unprecedented morphological detail in intact biological tissue. Using the isSID assay, we confirm seeding activity in α-syn aggregates in PD, MSA, and other proteinopathies, while uncovering neuron-driven seeding preceding the clinical symptom onset in PD. Our findings provide new fundamental insights into the pathogenesis underlying neurodegeneration and establish an invaluable tool for studying protein aggregation dynamics, with potential applications in biomarker discovery, diagnostics, and therapeutics.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"22 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899289","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

Supplementary motor area microstructure defines the extent of gait impairment in Parkinson’s disease 辅助运动区微结构定义帕金森病步态损害的程度

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-25 DOI: 10.1038/s41531-025-01119-4

Paweł P. Wróbel, Annika Peter, Maja Kirsten, Alessandro Gulberti, Maxim Bester, Einar Goebell, Bastian Cheng, Yogesh Rathi, Ofer Pasternak, Tim Magnus, Götz Thomalla, Fanny Quandt, Robert Schulz, Focko L. Higgen, Monika Pötter-Nerger

{"title":"Supplementary motor area microstructure defines the extent of gait impairment in Parkinson’s disease","authors":"Paweł P. Wróbel, Annika Peter, Maja Kirsten, Alessandro Gulberti, Maxim Bester, Einar Goebell, Bastian Cheng, Yogesh Rathi, Ofer Pasternak, Tim Magnus, Götz Thomalla, Fanny Quandt, Robert Schulz, Focko L. Higgen, Monika Pötter-Nerger","doi":"10.1038/s41531-025-01119-4","DOIUrl":"https://doi.org/10.1038/s41531-025-01119-4","url":null,"abstract":"Gait disorders and freezing of gait are challenging symptoms in Parkinson’s disease. Cortical gait centers as the supplementary motor area appear to be relevant in gait control. We hypothesize that diffusion-MRI microstructural markers in this area are associated with quantitative gait performance in participants with Parkinson’s Disease. Retrospective clinical data showed that lower fractional anisotropy in the right supplementary motor cortex was associated with better performance in various bilateral quantitative gait parameters at normal speed, maximal velocity, and especially during cognitively demanding conditions as dual-tasking. Gait performance did not correlate with cortical thickness. In contrast, the correlation between gait and microstructure in the supplementary motor area could indicate that diffusion-MRI might function as a clinical biomarker. The added value might support the clinical prognosis and aid in the development of new interventions, such as localized and personalized stimulation techniques.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"47 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899290","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

Synthetic MRI study of brain volume and subcortical myelin in various Parkinson’s disease motor subtypes 不同帕金森病运动亚型脑容量和皮质下髓磷脂的合成MRI研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-23 DOI: 10.1038/s41531-025-01120-x

Dongliang Cheng, Junyan Wen, Nan Ding, Zhenpeng Duan, Biqing Lin, Yunjun Yang, Yaozhong Wu, Hang Wang, Jincheng Ma, Jialu Zhang, Zhifeng Xu, Hai Zhao, Yulin Liu, Ge Wen

{"title":"Synthetic MRI study of brain volume and subcortical myelin in various Parkinson’s disease motor subtypes","authors":"Dongliang Cheng, Junyan Wen, Nan Ding, Zhenpeng Duan, Biqing Lin, Yunjun Yang, Yaozhong Wu, Hang Wang, Jincheng Ma, Jialu Zhang, Zhifeng Xu, Hai Zhao, Yulin Liu, Ge Wen","doi":"10.1038/s41531-025-01120-x","DOIUrl":"https://doi.org/10.1038/s41531-025-01120-x","url":null,"abstract":"Alterations in brain volume and subcortical myelin content (MyC) between tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes of Parkinson’s (PD) disease remain unclear. This study investigated whole-brain volume and subcortical myelin content differences among PD motor subtypes using synthetic MRI. Ninety-two PD patients (39 TD and 53 PIGD) and 39 healthy controls were included. ANCOVA identified that PD patients exhibited reduced gray matter, white matter, and MyC, with no distinct atrophy patterns between TD and PIGD. Most subcortical nuclei showed decreased myelin, while PIGD presented more extensive alterations and increased bilateral caudate myelin; TD exhibited asymmetric thalamic myelin changes, with lateralized increases and decreases. Significant MyC differences in the left caudate and right GPi were observed between TD and PIGD. Synthetic MRI-derived parameters provide insights into whole-brain atrophy patterns and dynamic myelin changes in PD, contributing to a deeper understanding of PD subtypes.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899566","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

New perspectives on molecular mechanisms underlying exercise-induced benefits in Parkinson’s disease 帕金森病运动诱导益处的分子机制新观点

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-23 DOI: 10.1038/s41531-025-01113-w

Xingyue Chen, Guoxin Zhang, Miao Liu, Juanfeng He, Zhentao Zhang

引用次数: 0

Brain-region-specific lipid dysregulation in L-DOPA-induced dyskinesia in a primate model of Parkinson’s disease 帕金森病灵长类动物模型中左旋多巴诱导的运动障碍的脑区域特异性脂质失调

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-23 DOI: 10.1038/s41531-025-01109-6

Ibrahim Kaya, Theodosia Vallianatou, Anna Nilsson, Patrik Bjärterot, Reza Shariatgorji, Per Svenningsson, Erwan Bezard, Per E. Andrén

{"title":"Brain-region-specific lipid dysregulation in L-DOPA-induced dyskinesia in a primate model of Parkinson’s disease","authors":"Ibrahim Kaya, Theodosia Vallianatou, Anna Nilsson, Patrik Bjärterot, Reza Shariatgorji, Per Svenningsson, Erwan Bezard, Per E. Andrén","doi":"10.1038/s41531-025-01109-6","DOIUrl":"https://doi.org/10.1038/s41531-025-01109-6","url":null,"abstract":"L-DOPA-induced dyskinesia (LID) is a significant and treatment-limiting complication in Parkinson’s disease (PD) therapy, yet its mechanisms remain poorly understood. We used high-resolution mass spectrometry imaging to map brain-region-specific alterations of glycerophospholipids and sphingolipids in a female macaque model of PD with and without LID following chronic L-DOPA treatment. LID was associated with depletion of antioxidant plasmalogen phosphatidylcholines in the globus pallidus interna, claustrum, and precentral gyrus—regions critical for motor function—and elevations of polyunsaturated fatty acid-containing glycerophospholipids, indicative of increased membrane fluidity. This lipid profile differed from similarly treated non-dyskinetic animals, suggesting lipid composition mediates differential susceptibility to LID. Lipid alterations correlated strongly with dyskinesia severity, dopamine, and L-DOPA concentrations, supporting a mechanistic link between lipid metabolism, neurotransmitter dysregulation, and LID. This comprehensive spatial lipidomic analysis identifies region-specific lipid dysregulation as a novel aspect of LID pathology, highlighting lipid pathways as potential therapeutic targets for mitigating dyskinesia.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"31 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899567","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

Alterations of the skin microbiome in multiple system atrophy: a pilot study 多系统萎缩中皮肤微生物组的改变：一项初步研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-23 DOI: 10.1038/s41531-025-01121-w

Daji Chen, Lang Sun, Linlin Wan, Zhao Chen, LinLiu Peng, Jinzi Peng, Riwei Ouyang, Xiafei Long, Kefang Du, Xiao Dong, Xiaokang Wu, Xinying Xiao, Ruqing He, Rong Qiu, Beisha Tang, Hong Jiang

引用次数: 0