NPJ Parkinson's Disease最新文献

Dopamine amplifies subthalamic long-latency responses to cortical stimulation in patients with Parkinson's disease. 多巴胺增强帕金森病患者丘脑下对皮质刺激的长潜伏期反应。

IF 8.5 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-19 DOI: 10.1038/s41531-026-01567-6

Jean-Christin Beyer, Alessia Cavallo, Jojo Vanhoecke, Richard M Köhler, Bassam Al-Fatly, Gerd-Helge Schneider, Katharina Faust, Gregor A Brandt, Andrea A Kühn, Wolf-Julian Neumann

{"title":"Dopamine amplifies subthalamic long-latency responses to cortical stimulation in patients with Parkinson's disease.","authors":"Jean-Christin Beyer, Alessia Cavallo, Jojo Vanhoecke, Richard M Köhler, Bassam Al-Fatly, Gerd-Helge Schneider, Katharina Faust, Gregor A Brandt, Andrea A Kühn, Wolf-Julian Neumann","doi":"10.1038/s41531-026-01567-6","DOIUrl":"https://doi.org/10.1038/s41531-026-01567-6","url":null,"abstract":"The cortico-subthalamic hyperdirect pathway provides a rapid route for cortical influence over basal ganglia processing and is a key target of deep brain stimulation (DBS) in Parkinson's disease (PD). However, to what degree dopamine modulates signal transmission along this pathway in humans remains unclear. Using bidirectional cortical and subthalamic electrical stimulation while invasively recording evoked responses in 15 PD patients undergoing DBS surgery, we examined cortico-subthalamic communication across dopaminergic states. Cortical stimulation evoked a short-latency subthalamic response consistent with monosynaptic hyperdirect activation that was preserved across medication conditions. In contrast, longer-latency subthalamic responses showed significant dopaminergic modulation, while cortical responses to subthalamic stimulation remained unchanged. These results reveal a temporal dissociation within the cortex-basal ganglia network, whereby fast cortical transmission is unaffected by dopamine, which in turn amplifies slower network level communication to the subthalamic nucleus. This separation of fast and delayed components provides a mechanistic framework for understanding how dopamine shapes information flow in the cortex-basal ganglia system.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224322","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

Computer vision, Parkinson’s disease, and the unfinished work of clinical translation 计算机视觉，帕金森氏症，以及未完成的临床翻译工作

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-18 DOI: 10.1038/s41531-026-01577-4

Jane Alty,Maximilian U. Friedrich

引用次数: 0

Clinical, neuroimaging, and longitudinal progression characteristics of GBA1-associated Parkinson’s disease in a Northeast China cohort 中国东北地区gba1相关帕金森病的临床、神经影像学和纵向进展特征

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-15 DOI: 10.1038/s41531-026-01597-0

Xiaoxiao Du,Xinyu Wang,Pingping Shen,Yue Liang,Xiaoyue Lin,Jun Chen,Lin Pan,Ying Zhang

引用次数: 0

A distinct immunometabolic signature defines early-stage Parkinson’s disease with Alzheimer’s disease co-pathology 一种独特的免疫代谢特征定义了早期帕金森病与阿尔茨海默病的共同病理

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-15 DOI: 10.1038/s41531-026-01594-3

Davide Mascioli,Valentina Nesci,Federica Veltri,Jacopo Bissacco,Eugenia Di Liberto,Clara Simonetta,Maria Mancini,Veronica Buttarazzi,Matteo Conti,Marco Rosina,Daniela Maftei,Giulia Maria Sancesario,Giulia Carrera,Veronica Ceci,Stefano Saracini,Alessandro Stefani,Mariangela Pierantozzi,Diego Centonze,Cristiana Valle,Alberto Ferri,Valerio Chiurchiù,Tommaso Schirinzi

引用次数: 0

Multi-omics analysis of hypoxia-mitochondrial energy metabolism and programmed cell death profiling in Parkinson’s disease 帕金森病缺氧-线粒体能量代谢和程序性细胞死亡谱的多组学分析

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-13 DOI: 10.1038/s41531-026-01576-5

An Chang,Yi Wu,Piaopiao Lian,Zhuoran Ma,Zhicheng Tang,Haoxuan Ouyang,Maoyu Liu,Xuebing Cao,Heng Zhai,Yan Xu

{"title":"Multi-omics analysis of hypoxia-mitochondrial energy metabolism and programmed cell death profiling in Parkinson’s disease","authors":"An Chang,Yi Wu,Piaopiao Lian,Zhuoran Ma,Zhicheng Tang,Haoxuan Ouyang,Maoyu Liu,Xuebing Cao,Heng Zhai,Yan Xu","doi":"10.1038/s41531-026-01576-5","DOIUrl":"https://doi.org/10.1038/s41531-026-01576-5","url":null,"abstract":"Abstract Hypoxia and mitochondrial energy metabolism (MEM) impairment are pivotal features of Parkinson’s disease (PD), yet the regulators linking hypoxic stress to mitochondrial failure remain elusive. Here we integrated multiple transcriptomic datasets from the substantia nigra to characterize the hypoxia and MEM landscape. Utilizing a tripartite machine learning framework combined with LASSO-logistic regression, we developed a robust seven-gene diagnostic model that achieved high predictive accuracy (AUC: 0.887 training; 0.821 validation). Two-sample Mendelian randomization (MR) analysis further identified seven causal genes (TTC19, SERPINA1, MPC2, DLK1, DDIT4, AUH, and ASL) associated with PD risk. By integrating programmed cell death (PCD) profiling and scRNA-seq, we discovered that core regulators MPC2 and AUH were uniquely associated with novel PCD modes, showing negative correlations with alkaliptosis and positive correlations with cuproptosis. Single-cell analysis localized primary hypoxia-MEM impairment to dopaminergic neurons (DaNs), where MPC2 expression was significantly depleted. In silico virtual knockout of MPC2 disrupted dopamine metabolism and synaptic vesicle cycles, while STAT3 and MEF2A were identified as potential upstream transcription factors linking metabolic dysfunction to neuroinflammation. Together, our findings identify MPC2 as a genetically supported causal regulator linking hypoxia-MEM failure to novel PCD in DaNs, offering potential biomarkers and therapeutic targets for precision intervention in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208770","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

Striatal network dysfunction underlying speech impairment in early Parkinson's disease. 纹状体网络功能障碍是早期帕金森病言语障碍的基础。

IF 8.5 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-12 DOI: 10.1038/s41531-026-01509-2

Caitlin Paige Rogers, Sandy Mournet, Cécile Gallea, Emma Biondetti, Graziella Mangone, Sara Sambin, Lydia Chougar, Nicolas Villain, Rahul Gaurav, Isabelle Arnulf, Marie-Odile Habert, Dijana Petrovska-Delacrétaz, Jean-Christophe Corvol, Habib Benali, Marie Vidailhet, Stéphane Lehéricy, Laetitia Jeancolas

{"title":"Striatal network dysfunction underlying speech impairment in early Parkinson's disease.","authors":"Caitlin Paige Rogers, Sandy Mournet, Cécile Gallea, Emma Biondetti, Graziella Mangone, Sara Sambin, Lydia Chougar, Nicolas Villain, Rahul Gaurav, Isabelle Arnulf, Marie-Odile Habert, Dijana Petrovska-Delacrétaz, Jean-Christophe Corvol, Habib Benali, Marie Vidailhet, Stéphane Lehéricy, Laetitia Jeancolas","doi":"10.1038/s41531-026-01509-2","DOIUrl":"10.1038/s41531-026-01509-2","url":null,"abstract":"The pathophysiology underlying Parkinson's disease (PD) speech impairments and its potential sex differences remain unclear. We investigated sex-specific alterations in speech and striato-cortical networks in 104 patients with early PD (68M/36F), and 44 healthy controls (23M/21F), using quantitative speech markers and multimodal neuroimaging. Speech features related to prosody, phonation, articulation, fluency, and rhythm, were extracted from voice recordings; striatal dopaminergic loss was quantified using DaT-SPECT, and functional connectivity between striatal and cortical language networks was analyzed with resting-state fMRI. Results showed that PD-related speech impairments were more pronounced in males. Functional connectivity was globally reduced in PD, but female patients exhibited higher caudate-cortical connectivity. In males, speech deficits were associated with both dopaminergic loss and connectivity disruption, whereas in females, only connectivity changes were involved. These findings revealed sex-specific pathophysiological mechanisms in early PD speech disorders, emphasizing the need for sex-stratified approaches in research and clinical practice.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A ‘brain-first’ mouse model of progressive alpha-synuclein pathology via intranasal rotenone administration 通过鼻内给药鱼藤酮建立进行性α -突触核蛋白病理的“脑优先”小鼠模型

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-08 DOI: 10.1038/s41531-026-01593-4

Monika Sharma,Nishant Sharma,Jhanvi Soni,Manasi Uttarkar,Jana Ruda-Kucerova,Tiago F. Outeiro,Irena Rektorova,Amit Khairnar

引用次数: 0

Multi-omics of host–gut metabolic crosstalk in Parkinson’s disease 帕金森病宿主-肠道代谢串扰的多组学研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-05 DOI: 10.1038/s41531-026-01561-y

Tzi Shin Toh, Chun Wie Chong, Mun Fai Loke, Lei Cheng Lit, Vimala Balakrishnan, Zhuangzhuang Pan, Sze Looi Song, Cindy Shuan Ju Teh, Shen-Yang Lim, Ai Huey Tan

{"title":"Multi-omics of host–gut metabolic crosstalk in Parkinson’s disease","authors":"Tzi Shin Toh, Chun Wie Chong, Mun Fai Loke, Lei Cheng Lit, Vimala Balakrishnan, Zhuangzhuang Pan, Sze Looi Song, Cindy Shuan Ju Teh, Shen-Yang Lim, Ai Huey Tan","doi":"10.1038/s41531-026-01561-y","DOIUrl":"https://doi.org/10.1038/s41531-026-01561-y","url":null,"abstract":"An altered gut microbiome has been implicated in Parkinson’s disease (PD), yet its reciprocal effects on systemic metabolism remain unclear. This cross-sectional study included 67 PD patients and 64 non-PD controls and integrated untargeted serum and fecal metabolomics using liquid chromatography-mass spectrometry with 16S rRNA gene sequencing of the gut microbiome. PD patients exhibited lipid dysregulation, including alterations in serum isoprenoids and their bacteria-derived precursor (2-C-methyl-D-erythritol 4-phosphate), sphingolipids, and glycerophospholipids, with perturbations in fatty acid biosynthesis pathways. Multi-omics integration revealed that PD was more closely associated with gut microbiome and serum metabolomics. Serum N-hydroxy-L-phenylalanine was linked to hydrogen sulfide-producing Desulfovibrio, implicating microbial-related amino acid metabolism. Machine learning models predicted cognition in PD more robustly than motor impairment and were driven exclusively by gut-derived features, including short-chain fatty acid-producing taxa, opportunistic pathogens, and fecal lipid metabolites, whereas no serum metabolites contributed. These findings highlight novel microbial-driven lipid and amino acid pathways with potential biomarker and therapeutic relevance in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087807","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 subcortical structures are associated with anxiety in early Parkinson’s disease patients: a cross-sectional 7T MRI study 皮层下结构的改变与早期帕金森病患者的焦虑有关：一项横断面7T MRI研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-03 DOI: 10.1038/s41531-026-01532-3

Guillaume Carey, Michiel van Lier, Stijn Michielse, Amée F. Wolters, Kathy Dujardin, Mark L. Kuijf, Albert F. G. Leentjens

{"title":"Alterations of subcortical structures are associated with anxiety in early Parkinson’s disease patients: a cross-sectional 7T MRI study","authors":"Guillaume Carey, Michiel van Lier, Stijn Michielse, Amée F. Wolters, Kathy Dujardin, Mark L. Kuijf, Albert F. G. Leentjens","doi":"10.1038/s41531-026-01532-3","DOIUrl":"https://doi.org/10.1038/s41531-026-01532-3","url":null,"abstract":"Anxiety is a prevalent non-motor symptom in Parkinson’s disease (PD), yet its neurobiological markers remain poorly understood. This study aimed to identify volumetric and morphological changes in subcortical structures associated with anxiety in early PD. In this cross-sectional study from the TRACK-PD cohort (Dutch Trial Register - NL7558), 105 non-demented PD patients (31 with anxiety [AnxPD], 74 without [nonAnxPD]) and 37 healthy controls (HC) underwent 7 T MRI. Subcortical regions including the amygdala, hippocampus, accumbens, caudate, putamen, and thalamus were segmented using FastSurfer. Shape analyses were performed via the Spherical Harmonics Point Distribution Model (SPHARM-PDM). Anxiety severity in PD was significantly associated with a bilateral reduction in caudate volume. Furthermore, AnxPD patients exhibited distinct shape deformations in the bilateral caudate, bilateral thalamus, left nucleus accumbens, and left amygdala compared to non-anxious patients. Significant shape differences in the left amygdala and left thalamus were also observed between AnxPD and HC groups. PD-related anxiety is linked to distinct structural remodeling of the striatum, thalamus, and amygdala. These morphometric changes represent potential imaging markers for the occurrence and progression of anxiety in early PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"166 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087624","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

Interpretable survival prediction in Parkinson’s disease with AI-assisted web deployment 人工智能辅助网络部署对帕金森病可解释的生存预测

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2026-10-03 DOI: 10.1038/s41531-026-01589-0

Tingwei Song, Yuan Liu, Linghui Xiang, Hongxu Pan, Yiting Wu, Xiaoyun Li, Fei Luo, Chunyu Wang, Lifang Lei, Lingyan Yao, Yuwen Zhao, Zhenhua Liu, Qiying Sun, Jifeng Guo, Beisha Tang, Xiaoxia Zhou, Li Yin, Irene X. Y. Wu, Qian Xu, and for Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)

{"title":"Interpretable survival prediction in Parkinson’s disease with AI-assisted web deployment","authors":"Tingwei Song, Yuan Liu, Linghui Xiang, Hongxu Pan, Yiting Wu, Xiaoyun Li, Fei Luo, Chunyu Wang, Lifang Lei, Lingyan Yao, Yuwen Zhao, Zhenhua Liu, Qiying Sun, Jifeng Guo, Beisha Tang, Xiaoxia Zhou, Li Yin, Irene X. Y. Wu, Qian Xu, and for Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)","doi":"10.1038/s41531-026-01589-0","DOIUrl":"https://doi.org/10.1038/s41531-026-01589-0","url":null,"abstract":"Survival prediction in Parkinson’s disease (PD) remains limited, and few models have been translated into reproducible web-based tools. We analyzed 3148 patients with PD from the Chinese Parkinson’s Disease Registry, enrolled at 19 tertiary hospitals between 2018 and 2020 and followed through December 31, 2024. Cox regression, random survival forest, survival tree, and XGBoost survival models were compared using repeated five-fold cross-validation with multiple imputation performed within training folds. The final Cox model was fitted across 20 completed datasets, pooled using Rubin’s rules, and evaluated using split-first temporal validation. The 11 predictors retained in the final model covered demographic, genetic, treatment-related, motor, and non-motor domains. Cox, random survival forest, and XGBoost showed similar discrimination, with mean C-index values of 0.716 for all three models, whereas the survival tree performed lower, with a mean C-index of 0.690. For the deployed Cox model, the mean 2-, 4-, and 6-year AUCs were 0.713, 0.726, and 0.750. In temporal validation, the C-index was 0.708, with modest underestimation of absolute mortality risk. The selected Cox model was implemented in a web platform providing individualized survival estimates, with language-model modules limited to structured data entry and general PD education.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087626","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