NPJ Parkinson's Disease最新文献_第2页

Cerebral perfusion imaging predicts levodopa-induced dyskinesia in Parkinsonian rat model. 脑灌注成像预测帕金森大鼠左旋多巴诱导的运动障碍。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-30 DOI: 10.1038/s41531-025-01133-6

Jarrad Perron,Sophia Krak,Samuel Booth,Dali Zhang,Ji Hyun Ko

{"title":"Cerebral perfusion imaging predicts levodopa-induced dyskinesia in Parkinsonian rat model.","authors":"Jarrad Perron,Sophia Krak,Samuel Booth,Dali Zhang,Ji Hyun Ko","doi":"10.1038/s41531-025-01133-6","DOIUrl":"https://doi.org/10.1038/s41531-025-01133-6","url":null,"abstract":"Many Parkinson's disease (PD) patients manifest complications related to treatment called levodopa-induced dyskinesia (LID). Preventing the onset of LID is crucial to the management of PD, but the reasons why some patients develop LID are unclear. The ability to prognosticate predisposition to LID would be valuable for the investigation of mitigation strategies. Thirty rats received 6-hydroxydopamine to induce Parkinsonism-like behaviors before treatment with levodopa (2 mg/kg) daily for 22 days. Fourteen developed LID-like behaviors. Fluorodeoxyglucose PET, T2-weighted MRI and cerebral perfusion imaging were collected before treatment. Support vector machines were trained to classify prospective LID vs. non-LID animals from treatment-naïve baseline imaging. Volumetric perfusion imaging performed best overall with 86.16% area-under-curve, 86.67% accuracy, 92.86% sensitivity, and 81.25% specificity for classifying animals with LID vs. non-LID in leave-one-out cross-validation. We have demonstrated proof-of-concept for imaging-based classification of susceptibility to LID of a Parkinsonian rat model using perfusion-based imaging and a machine learning model.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"102 1","pages":"278"},"PeriodicalIF":8.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194955","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

Proteolytic activities of extracellular vesicles attenuate A-synuclein aggregation. 细胞外囊泡的蛋白水解活性减弱了A-synuclein聚集。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-29 DOI: 10.1038/s41531-025-01122-9

Kostas Vekrellis,Agaristi Lamprokostopoulou,Katerina Melachroinou,Marianna Kokoli,Eleni Zingkou,Marina Skarveli,Asimina Kolianou,Martina Samiotaki,Georgia Sotiropoulou

{"title":"Proteolytic activities of extracellular vesicles attenuate A-synuclein aggregation.","authors":"Kostas Vekrellis,Agaristi Lamprokostopoulou,Katerina Melachroinou,Marianna Kokoli,Eleni Zingkou,Marina Skarveli,Asimina Kolianou,Martina Samiotaki,Georgia Sotiropoulou","doi":"10.1038/s41531-025-01122-9","DOIUrl":"https://doi.org/10.1038/s41531-025-01122-9","url":null,"abstract":"Extracellular vesicles (EVs) are nano-sized lipid vesicles released into the extracellular space. We investigated the role of mouse brain-derived EVs in α-synuclein (α-syn) degradation and pathology transmission. Using sucrose gradient isolation and biochemical characterization, we found that EVs harbor active proteases that cleave both monomeric α-syn and pre-formed fibrils (PFFs). Protease activity and inhibitor profiling identified cathepsins B and S as key enzymes mediating this cleavage. EV-mediated proteolysis reduced the seeding capacity of α-syn PFFs in vitro and in vivo, whereas protease inhibition enhanced aggregation. Proteomic analysis revealed a restricted protease repertoire within EV cargo. Our findings suggest that EVs regulate extracellular α-syn levels via proteolysis, thereby modulating its prion-like spreading potential. We suggest that EVs represent a novel post-translational mechanism to regulate the levels of extracellular α-syn and may thus affect the spreading of α-syn pathology. Targeting this proteolytic capacity may offer new therapeutic interventions for mitigating synucleinopathies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"157 1","pages":"277"},"PeriodicalIF":8.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188431","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

Sleep stage mixing is associated with poor prognosis in early Parkinson's disease. 睡眠阶段混杂与早期帕金森病预后不良相关。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-26 DOI: 10.1038/s41531-025-01105-w

Pauline Dodet,Emmanuel During,Isabelle Arnulf,Claudia Trenkwalder,Brit Mollenhauer,Friederike Sixel-Döring,Emmanuel Roze,Marie Vidailhet,Thomas Andrillon,Stéphane Lehericy,Jean-Christophe Corvol,Graziella Mangone,Smaranda Leu-Semenescu,Emmanuel Mignot,Poul Jennum,Andreas Brink-Kjaer

{"title":"Sleep stage mixing is associated with poor prognosis in early Parkinson's disease.","authors":"Pauline Dodet,Emmanuel During,Isabelle Arnulf,Claudia Trenkwalder,Brit Mollenhauer,Friederike Sixel-Döring,Emmanuel Roze,Marie Vidailhet,Thomas Andrillon,Stéphane Lehericy,Jean-Christophe Corvol,Graziella Mangone,Smaranda Leu-Semenescu,Emmanuel Mignot,Poul Jennum,Andreas Brink-Kjaer","doi":"10.1038/s41531-025-01105-w","DOIUrl":"https://doi.org/10.1038/s41531-025-01105-w","url":null,"abstract":"This study assessed the prognostic value of probabilistic sleep staging in early PD by quantifying sleep stage uncertainty and mixing. Data from two longitudinal cohorts (DeNoPa and ICEBERG) included 280 patients with early PD (mean duration 21.1 months) and 158 matched controls. Sleep stages were scored automatically using U-Sleep, which provides for each 30-s epoch a probabilistic distribution of wakefulness (W), NREM stage N1, N2, N3, and REM sleep. Uncertainty (percentage of sleep stages with less than 80% certainty) and mixed stages were quantified. PD patients showed higher sleep stage uncertainty and wake-N3 mixing, especially those with REM sleep behavior disorder. Greater W-N3 mixing was associated with worse motor and cognitive scores at baseline and with faster motor decline over time. EEG features of this mixing suggested unstable deep sleep. These findings support the value of automated sleep analysis to detect microstructural sleep disruptions linked to PD progression.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":"275"},"PeriodicalIF":8.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153456","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

N-type Ca2+ channels mediate the stimuli-dependent α-synuclein secretion in mouse striatum. n型Ca2+通道介导小鼠纹状体刺激依赖性α-突触核蛋白分泌。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-26 DOI: 10.1038/s41531-025-01110-z

Emmanouela Leandrou,Ioanna Chalatsa,Kostas Vekrellis,Evangelia Emmanouilidou

引用次数: 0

Independent serum metabolomics approaches identify disrupted glutamic acid and serine metabolism in Parkinson's disease patients. 独立的血清代谢组学方法鉴定帕金森病患者谷氨酸和丝氨酸代谢紊乱。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-25 DOI: 10.1038/s41531-025-01126-5

Jacopo Gervasoni, Carmen Marino, Alberto Imarisio, Lavinia Santucci, Enza Napolitano, Tommaso Nuzzo, Isar Yahyavi, Micol Avenali, Michela Cicchinelli, Gabriele Buongarzone, Caterina Galandra, Marta Picascia, Manuela Grimaldi, Claudio Pacchetti, Francesco Errico, Anna Maria D'Ursi, Andrea Urbani, Enza Maria Valente, Alessandro Usiello

引用次数: 0

Genome-wide association study of REM sleep behavior disorder in Parkinson's disease. 帕金森病快速眼动睡眠行为障碍的全基因组关联研究

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-25 DOI: 10.1038/s41531-025-01078-w

Yuri L Sosero, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe-Kaufmann, Eric Yu, Uladzislau Rudakou, Jennifer A Ruskey, Kathryn Freeman, Farnaz Asayesh, Kajsa A Brolin, Maria Swanberg, Huw R Morris, Lesley Wu, Raquel Real, Lasse Pihlstrøm, Manuela Tan, Thomas Gasser, Kathrin Brockmann, Hui Liu, Michele T M Hu, Donald G Grosset, Simon J G Lewis, John B Kwok, Pau Pastor, Ignacio Alvarez, Matej Skorvanek, Alexandra Lackova, Miriam Ostrozovicova, Mie Rizig, Lynne Krohn, Ziv Gan-Or

{"title":"Genome-wide association study of REM sleep behavior disorder in Parkinson's disease.","authors":"Yuri L Sosero, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe-Kaufmann, Eric Yu, Uladzislau Rudakou, Jennifer A Ruskey, Kathryn Freeman, Farnaz Asayesh, Kajsa A Brolin, Maria Swanberg, Huw R Morris, Lesley Wu, Raquel Real, Lasse Pihlstrøm, Manuela Tan, Thomas Gasser, Kathrin Brockmann, Hui Liu, Michele T M Hu, Donald G Grosset, Simon J G Lewis, John B Kwok, Pau Pastor, Ignacio Alvarez, Matej Skorvanek, Alexandra Lackova, Miriam Ostrozovicova, Mie Rizig, Lynne Krohn, Ziv Gan-Or","doi":"10.1038/s41531-025-01078-w","DOIUrl":"10.1038/s41531-025-01078-w","url":null,"abstract":"REM sleep behavior disorder (RBD), is a prodromal synucleinopathy affecting a subset of Parkinson's disease (PD) patients and associated with neuropsychiatric symptoms. This study compared the genetic profiles of 13,020 PD patients with probable RBD (PD + RBD) and 5403 without (PD-RBD) using genome-wide association study (GWAS). RBD was assessed by questionnaires or self-reporting. Potential genetic correlations between neuropsychiatric traits and PD + RBD were assessed using linkage disequilibrium score regression. The top variant in the SNCA locus was associated with PD + RBD (rs10005233-T, OR = 1.21, 95% CI = 1.16-1.27, p = 1.81e-15). PD risk variants in SNCA (rs5019538-G, OR = 0.85, 95% CI = 0.81-0.89, p = 2.46e-10; rs356182-G, OR = 0.89, 95% CI = 0.84-0.95, p = 0.0001) and LRRK2 loci (rs34637584, OR = 0.41, 95% CI = 0.28-0.61, p = 1.04e-5) were associated with reduced PD + RBD risk. A suggestive genetic correlation between attention deficit hyperactivity disorder and PD + RBD was observed but was not statistically significant after correction. These findings highlight genetic distinctions between PD + RBD and PD-RBD, offering insights into PD stratification and potential subtype-specific treatments.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":"272"},"PeriodicalIF":8.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150337","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

Predicting Parkinson's disease and its progression based on radiomics in T1-weight images and α‑synuclein in cerebrospinal fluid. 基于t1体重图像和脑脊液α -突触核蛋白放射组学预测帕金森病及其进展。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-25 DOI: 10.1038/s41531-025-01097-7

Xu Zhang,Hui Li,Xiaona Xia,Jiaojiao Wu,Feng Shi,Cuiping Zhao,Xiangshui Meng,Qingguo Ren

{"title":"Predicting Parkinson's disease and its progression based on radiomics in T1-weight images and α‑synuclein in cerebrospinal fluid.","authors":"Xu Zhang,Hui Li,Xiaona Xia,Jiaojiao Wu,Feng Shi,Cuiping Zhao,Xiangshui Meng,Qingguo Ren","doi":"10.1038/s41531-025-01097-7","DOIUrl":"https://doi.org/10.1038/s41531-025-01097-7","url":null,"abstract":"This study aimed to develop a radiomics model that can predict Parkinson's disease (PD) and its progression of using T1-weighted images (T1WI), and to evaluate the prediction performance of a multimodal model incorporating clinical factors. We selected all participants from the Parkinson's Progression Markers Initiative (PPMI) (n = 205) database and Qilu Hospital of Shandong University (Qingdao) (n = 60). The patients were tracked over 4-5 years via Hoehn-Yahr Scale (HYS) and categorized into stable PD (SPD: HYS unchanged) and progression PD (PPD: HYS increase). Participants from the PPMI database were randomly divided into a training dataset and an internal testing dataset to construct radiomics models, which were validated by the Qilu Hospital database as an independent testing dataset. Only participants from the PPMI database had cerebrospinal fluid (CSF) α‑synuclein (α-syn) data, which were used to establish a combined model. The radiomics-based classifier for healthy controls (HC) and PD achieved areas under the receiver operating characteristic curves (AUROCs) of 0.787 and 0.746 in the internal and independent testing datasets, respectively, while the AUROCs were 0.857 and 0.802 in predicting SPD and PPD, respectively. Moreover, integrating CSF total α-syn in the combined model enhanced the predictive performance, with AUROC of 0.890, sensitivity of 0.846 and specificity of 0.857 for HC vs. PD, and AUROC of 0.939, sensitivity of 0.917 and specificity of 0.933 for SPD vs. PPD in the internal testing dataset. The current research presented evidence that radiomics utilizing conventional T1WI can predict the clinical stages of PD and that the efficacy of the multimodal model can be boosted by combining radiomics with CSF total α‑syn.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"29 1","pages":"273"},"PeriodicalIF":8.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140305","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

Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide. 通过全d肽直接将α-syn预制原纤维分解成α-syn单体。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-22 DOI: 10.1038/s41531-025-01132-7

Marc Sevenich, Ian Gering, Bettina Kass, Madita Vollmer, Selma Aghabashlou Saisan, Markus Tusche, Tatsiana Kupreichyk, Thomas Pauly, Matthias Stoldt, Wolfgang Hoyer, Antje Willuweit, Janine Kutzsche, Nils-Alexander Lakomek, Luitgard Nagel-Steger, Lothar Gremer, Gültekin Tamgüney, Jeannine Mohrlüder, Dieter Willbold

{"title":"Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide.","authors":"Marc Sevenich, Ian Gering, Bettina Kass, Madita Vollmer, Selma Aghabashlou Saisan, Markus Tusche, Tatsiana Kupreichyk, Thomas Pauly, Matthias Stoldt, Wolfgang Hoyer, Antje Willuweit, Janine Kutzsche, Nils-Alexander Lakomek, Luitgard Nagel-Steger, Lothar Gremer, Gültekin Tamgüney, Jeannine Mohrlüder, Dieter Willbold","doi":"10.1038/s41531-025-01132-7","DOIUrl":"10.1038/s41531-025-01132-7","url":null,"abstract":"A hallmark of Parkinson's disease (PD) is the progressive neurodegeneration associated with soluble oligomeric and fibrillar forms of misfolded α-synuclein (α-syn). In this study, all-D-enantiomeric peptide ligands are presented that bind monomeric α-syn with high affinity, stabilize its physiological monomeric status, prevent aggregation and dissolve existing aggregates. This \"antiprionic\" mode of action directly targets pathogenic aggregated particles. Using mirror-image phage display on D-enantiomeric full-length α-syn, SVD-1 and SVD-1a were identified, showing a delay of aggregation and reduction of aggregate formation in both de novo and seeded models. Picomolar KDs were confirmed by SPR, where a highly dynamic interaction mode was verified by PRE-NMR. SVD-1a also reduced the toxicity and intracellular seeding of α-syn fibrils in cell culture by disassembling them into monomers, as confirmed by atomic force microscopy and dynamic light scattering. These results support SVD-1a as a promising lead compound for the treatment of Parkinson's disease.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":"271"},"PeriodicalIF":8.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125697","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

Methodological validation of Miro1 retention as a candidate Parkinson’s disease biomarker Miro1保留作为候选帕金森病生物标志物的方法学验证

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-09-15 DOI: 10.1038/s41531-025-01115-8

Layla Drwesh, Giuseppe Arena, Daniel J. Merk, Daniele Ferrante, Vyron Gorgogietas, Thomas Gasser, Anne Grünewald, Patrick May, Kathrin Brockmann, Rejko Krüger, Richard Wüst, Christian Johannes Gloeckner, Julia C. Fitzgerald

引用次数: 0

Author Correction: Patterns of cerebellar cortex hypermetabolism on motor and cognitive functions in PD. 作者更正：PD患者小脑皮质高代谢模式对运动和认知功能的影响。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-31 DOI: 10.1038/s41531-025-01131-8

Wen-Hua Ren, Bin Chen, Jiu-Qin He, Yu-Meng Qi, Ya-Yun Yan, Shu-Xian Jin, Ying Chang

引用次数: 0