NPJ Parkinson's Disease最新文献_第6页

A high-fidelity microfluidic platform reveals retrograde propagation as the main mechanism of α-Synuclein spread in human neurons 高保真微流控平台揭示了α-突触核蛋白在人神经元中逆行传播的主要机制

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-20 DOI: 10.1038/s41531-025-00936-x

Rozan Vroman, Lorenzo de Lichtervelde, Karamjit Singh Dolt, Graham Robertson, Marco Kriek, Michela Barbato, Justyna Cholewa-Waclaw, Tilo Kunath, Patrick Downey, Michele Zagnoni

{"title":"A high-fidelity microfluidic platform reveals retrograde propagation as the main mechanism of α-Synuclein spread in human neurons","authors":"Rozan Vroman, Lorenzo de Lichtervelde, Karamjit Singh Dolt, Graham Robertson, Marco Kriek, Michela Barbato, Justyna Cholewa-Waclaw, Tilo Kunath, Patrick Downey, Michele Zagnoni","doi":"10.1038/s41531-025-00936-x","DOIUrl":"https://doi.org/10.1038/s41531-025-00936-x","url":null,"abstract":"α-Synuclein (αSyn) is a major component of Lewy bodies and Lewy neurites, which are a pathological hallmark of Parkinson’s disease (PD). Pathologically aggregated forms of αSyn can spread along neurites and induce the misfolding of normal αSyn. To elucidate how αSyn pathology propagates between brain areas, we developed a novel in vitro microfluidic platform to study the intracellular transport of preformed fibrils and the induction and spread of αSyn aggregates. Patient-derived midbrain dopaminergic (mDA) neurons were cultured in microfluidic devices designed to maintain unidirectional axonal connections between fluidically isolated mDA neuronal cultures for over 3 months. Using αSyn preformed fibrils to induce Lewy-like pathology, we found that anterograde spread of αSyn fibrils was slow and occurred at low levels, while retrograde spread was significantly more efficient. This is in line with observations in animal models and shows that the platform provides an innovative new tool for studying PD in vitro.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853534","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

Detecting neuropsychiatric fluctuations in Parkinson’s Disease using patients’ own words: the potential of large language models 使用患者自己的语言来检测帕金森病的神经精神波动：大型语言模型的潜力

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-18 DOI: 10.1038/s41531-025-00939-8

Matilde Castelli, Mario Sousa, Illner Vojtech, Michael Single, Deborah Amstutz, Marie Elise Maradan-Gachet, Andreia D. Magalhães, Ines Debove, Jan Rusz, Pablo Martinez-Martin, Raphael Sznitman, Paul Krack, Tobias Nef

{"title":"Detecting neuropsychiatric fluctuations in Parkinson’s Disease using patients’ own words: the potential of large language models","authors":"Matilde Castelli, Mario Sousa, Illner Vojtech, Michael Single, Deborah Amstutz, Marie Elise Maradan-Gachet, Andreia D. Magalhães, Ines Debove, Jan Rusz, Pablo Martinez-Martin, Raphael Sznitman, Paul Krack, Tobias Nef","doi":"10.1038/s41531-025-00939-8","DOIUrl":"https://doi.org/10.1038/s41531-025-00939-8","url":null,"abstract":"Over the past decade, neuropsychiatric fluctuations in Parkinson’s disease (PD) have been increasingly recognized for their impact on patients’ quality of life. Speech, a complex function carrying motor, emotional, and cognitive information, offers potential insights into these fluctuations. While previous studies have focused on acoustic analysis to assess motor speech disorders reliably, the potential of linguistic patterns associated with neuropsychiatric fluctuations in PD remains unexplored. This study analyzed the content of spontaneous speech from 33 PD patients in ON and OFF medication states, using machine learning and large language models (LLMs) to predict medication states and a neuropsychiatric state score. The top-performing model, the LLM Gemma-2 (9B), achieved 98% accuracy in differentiating ON and OFF states and its predicted scores were highly correlated with actual scores (Spearman’s ρ = 0.81). These methods could provide a more comprehensive assessment of PD treatment effects, allowing remote neuropsychiatric symptom monitoring via mobile devices.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"29 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847115","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

Prioritizing Parkinson’s disease risk genes in genome-wide association loci 帕金森病风险基因在全基因组关联位点的优先排序

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-16 DOI: 10.1038/s41531-025-00933-0

Lara M. Lange, Catalina Cerquera-Cleves, Marijn Schipper, Georgia Panagiotaropoulou, Alice Braun, Julia Kraft, Swapnil Awasthi, Nathaniel Bell, Danielle Posthuma, Stephan Ripke, Cornelis Blauwendraat, Karl Heilbron

{"title":"Prioritizing Parkinson’s disease risk genes in genome-wide association loci","authors":"Lara M. Lange, Catalina Cerquera-Cleves, Marijn Schipper, Georgia Panagiotaropoulou, Alice Braun, Julia Kraft, Swapnil Awasthi, Nathaniel Bell, Danielle Posthuma, Stephan Ripke, Cornelis Blauwendraat, Karl Heilbron","doi":"10.1038/s41531-025-00933-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00933-0","url":null,"abstract":"Many drug targets in ongoing Parkinson’s disease (PD) clinical trials have strong genetic links. While genome-wide association studies (GWAS) nominate regions associated with disease, pinpointing causal genes is challenging. Our aim was to prioritize additional druggable genes underlying PD GWAS signals. The polygenic priority score (PoPS) integrates genome-wide information from MAGMA gene-level associations and over 57,000 gene-level features. We applied PoPS to East Asian and European PD GWAS data and prioritized genes based on PoPS, distance to the GWAS signal, and non-synonymous credible set variants. We prioritized 46 genes, including well-established PD genes (SNCA, LRRK2, GBA1, TMEM175, VPS13C), genes with strong literature evidence supporting a mechanistic link to PD (RIT2, BAG3, SCARB2, FYN, DYRK1A, NOD2, CTSB, SV2C, ITPKB), and genes relatively unexplored in PD. Many hold potential for drug repurposing or development. We prioritized high-confidence genes with strong links to PD pathogenesis that may represent our next-best candidates for developing disease-modifying therapeutics.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"29 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841262","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

Spatial variations and precise location of substantia nigra hyperechogenicity in Parkinson’s disease using TCS-MR fusion imaging TCS-MR融合成像在帕金森病黑质高回声的空间变化和精确定位

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-16 DOI: 10.1038/s41531-025-00910-7

Chao Hou, Wei Zhang, Hong-Bing Li, Shuo Li, Fang Nie, Xue-Mei Wang, Wen He

引用次数: 0

Exploring glymphatic system alterations in iRBD and Parkinson’s disease using automated DTI-ALPS analysis 利用自动DTI-ALPS分析探讨iRBD和帕金森病的淋巴系统改变

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-15 DOI: 10.1038/s41531-025-00921-4

S. Marecek, V. Rottova, J. Nepozitek, T. Krajca, R. Krupicka, J. Keller, D. Zogala, J. Trnka, K. Sonka, E. Ruzicka, P. Dusek

{"title":"Exploring glymphatic system alterations in iRBD and Parkinson’s disease using automated DTI-ALPS analysis","authors":"S. Marecek, V. Rottova, J. Nepozitek, T. Krajca, R. Krupicka, J. Keller, D. Zogala, J. Trnka, K. Sonka, E. Ruzicka, P. Dusek","doi":"10.1038/s41531-025-00921-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00921-4","url":null,"abstract":"Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a potential non-invasive marker of glymphatic function that typically relies on manual region of interest (ROI) placement. This study compared ALPS indices in treatment-naïve, de novo diagnosed patients with Parkinson’s disease (PD), patients with isolated REM behavior disorder (iRBD), and healthy controls using both manual and automatic approaches to the ROI selection used in ALPS-index calculation. ALPS indices were analyzed bilaterally and correlated with clinical severity (MDS-UPDRS) and nigrostriatal denervation (DAT-SPECT). ANCOVA revealed significant inter-group differences using both manual (p = 0.018) and automatic (p = 0.002) ROI selection methods. The automatic ROI selection approach showed significantly lower ALPS indices in PD compared to controls (p = 0.001) and iRBD (p = 0.009). ALPS indices correlated with symptom severity and nigrostriatal denervation. These findings underscore the reliability of the automatic ROI placement approach for ALPS index calculation and may indicate early glymphatic alterations in Parkinson’s disease.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"108 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836696","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

Additive effect of distant Lewy bodies and tau seeds injections on nigral degeneration in macaques 远处路易体和 tau 种子注射对猕猴黑质变性的叠加效应

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-13 DOI: 10.1038/s41531-025-00938-9

Morgane Darricau, Valentine Kulifaj, Marie-Laure Arotcarena, Qin Li, Taxiarchis Katsinelos, William A. McEwan, Maria Xilouri, Benjamin Dehay, Erwan Bezard, Vincent Planche

引用次数: 0

Linking Parkinson’s disease and melanoma: the impact of copper-driven cuproptosis and related mechanisms 帕金森病与黑色素瘤的联系：铜驱动的铜突起的影响及其相关机制

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-13 DOI: 10.1038/s41531-025-00928-x

Quan Wang, Yinghui Duan, Yu Xu, Hao Li, Yi Yang

引用次数: 0

Oral health implications in Parkinson’s disease 帕金森病对口腔健康的影响

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-11 DOI: 10.1038/s41531-025-00927-y

Xiaohui Qiu, Ran Zhang, Yi Cheng, Chengde Jin, Yushi Zhang, Ziqi Zhang

引用次数: 0

Mediterranean dietary pattern and risk of neurodegenerative diseases in a cohort of Swedish women 一组瑞典妇女的地中海饮食模式与神经退行性疾病的风险

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-11 DOI: 10.1038/s41531-025-00932-1

Emily E. Joyce, Weiyao Yin, Marie Löf, Karin Wirdefeldt, Sven Sandin, Fang Fang

引用次数: 0

Nigrostriatal iron accumulation in the progression of Parkinson’s disease 帕金森病进展中的黑质纹状体铁积累

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-11 DOI: 10.1038/s41531-025-00911-6

M. López-Aguirre, T. Balzano, M.H.G. Monje, N. Esteban-García, R. Martínez-Fernández, N.L. Del Rey, M. Ciorraga, A. Sánchez-Ferro, I. Trigo-Damas, J. Blesa, J. A. Obeso, J. A. Pineda-Pardo

{"title":"Nigrostriatal iron accumulation in the progression of Parkinson’s disease","authors":"M. López-Aguirre, T. Balzano, M.H.G. Monje, N. Esteban-García, R. Martínez-Fernández, N.L. Del Rey, M. Ciorraga, A. Sánchez-Ferro, I. Trigo-Damas, J. Blesa, J. A. Obeso, J. A. Pineda-Pardo","doi":"10.1038/s41531-025-00911-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00911-6","url":null,"abstract":"Iron deposition in the nigrostriatal system plays a pivotal role in Parkinson’s disease (PD) onset and progression. This study explored the time course of nigrostriatal iron accumulation in 54 PD patients at early to moderately advanced stages and 20 age-matched healthy controls. Using multi-echo T2*-MRI and R2* relaxometry, iron content was assessed in the substantia nigra pars compacta (SNpc) and striatum. In vivo findings were contrasted with histological analyses in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism model involving six non-human primates (NHPs) and two controls using Perls’ Prussian blue staining. Complementarily, dopaminergic degeneration was quantified by 6-[18F]-fluoro-L-dopa PET in humans and TH immunohistochemistry in NHPs. Results showed progressive iron accumulation in the SNpc correlating with striatal dopaminergic denervation and neuronal loss. Striatal iron followed a V-shaped progression, decreasing initially and increasing later. Iron in the SNpc may serve as a marker of neurodegeneration in PD, while decreased striatal iron may indicate pathological susceptibility to dopaminergic loss.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"108 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822771","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