NPJ Parkinson's Disease最新文献_第5页

Male sex accelerates cognitive decline in GBA1 Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-04 DOI: 10.1038/s41531-025-00883-7

Silvia Paola Caminiti, Micol Avenali, Alice Galli, Rachele Malito, Giada Cuconato, Caterina Galandra, Rosaria Calabrese, Andrea Pilotto, Alessandro Padovani, Fabio Blandini, Daniela Perani, Cristina Tassorelli, Enza Maria Valente

{"title":"Male sex accelerates cognitive decline in GBA1 Parkinson’s disease","authors":"Silvia Paola Caminiti, Micol Avenali, Alice Galli, Rachele Malito, Giada Cuconato, Caterina Galandra, Rosaria Calabrese, Andrea Pilotto, Alessandro Padovani, Fabio Blandini, Daniela Perani, Cristina Tassorelli, Enza Maria Valente","doi":"10.1038/s41531-025-00883-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00883-7","url":null,"abstract":"We evaluated 128 GBA and 432 nonGBA Parkinson’s disease (PD) subjects available from Parkinson’s Progression Markers Initiative. Baseline clinical features and dopaminergic activity were assessed, together with clinical follow-up (6.87 ± 3.2 years). Survival analyses assessed the independent and interactive effects of sex and GBA1 mutations on cognitive decline. At baseline, GBA-PD males showed severe motor impairment, sleep disorders and memory deficits. Despite milder motor deficit, compared to GBA-PD males, GBA-PD females showed greater dopaminergic denervation, suggesting the effect of neural reserve. In longitudinal assessment, GBA-PD males showed greater MoCA rate of change per year and greater risk of cognitive impairment than GBA-PD females and nonGBA-PD. In GBA-PD males, both late age at onset and “severe/mild” GBA variants were associated with increased risk of cognitive impairment. Male sex and GBA1 carrier status have an additive value in increasing the risk of cognitive decline in PD. The effect of sex on GBA1-related pathology warrants further examination to address future trials design and patients’ selection.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"17 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538438","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

Author Correction: A framework for translational therapy development in deep brain stimulation.

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-04 DOI: 10.1038/s41531-025-00890-8

Jiazhi Chen, Jens Volkmann, Chi Wang Ip

引用次数: 0

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: A DNA co-methylation network analysis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-02 DOI: 10.1038/s41531-025-00877-5

Joshua Harvey, Adam R. Smith, Luke S. Weymouth, Rebecca G. Smith, Isabel Castanho, Leon Hubbard, Byron Creese, Catherine Bresner, Nigel Williams, Ehsan Pishva, Katie Lunnon

引用次数: 0

Z/Ce@hemin enzymes with enhanced peroxidase activity for monitoring and screening the oxidative stress models of Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-01 DOI: 10.1038/s41531-025-00875-7

Li Lei, Xiuli Chen, Xincheng Long, Qiuxia Tu, Liping Zhao, Dan Huang, Lingli Song, Jiaojiao Wang, Suzhen Zhai, Xiaozhong Chen, Chunlin Zhang

{"title":"Z/Ce@hemin enzymes with enhanced peroxidase activity for monitoring and screening the oxidative stress models of Parkinson’s disease","authors":"Li Lei, Xiuli Chen, Xincheng Long, Qiuxia Tu, Liping Zhao, Dan Huang, Lingli Song, Jiaojiao Wang, Suzhen Zhai, Xiaozhong Chen, Chunlin Zhang","doi":"10.1038/s41531-025-00875-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00875-7","url":null,"abstract":"Inspired by natural enzymes, artificial enzymes have garnered significant interest due to their simplicity of production, robustness under harsh conditions, and enhanced stability. This study introduces, for the first time, a novel Z/Ce@hemin composite enzyme, constructed by anchoring hemin onto zeolitic imidazolate framework-8 (ZIF-8)-encapsulated ceria (CeO2) nanoparticles. This innovative design overcomes the challenges of hemin dimerization, enhances substrate affinity, and accelerates mass transport, leading to significantly improved peroxidase-like activity. The enzyme also demonstrates remarkable stability and resistance to environmental interference. Utilizing this Z/Ce@hemin composite, a sensitive and selective colorimetric detection system was developed for rapid and accurate quantification of hydrogen peroxide (H2O2), a key oxidative stress marker. This approach was successfully applied in cellular models and Caenorhabditis elegans models of Parkinson’s disease, enabling precise monitoring of H2O2. The study provides a groundbreaking platform for oxidative stress modeling and expands possibilities in neurodegenerative disease research and therapeutic screening.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"51 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526181","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

Transcutaneous auricular vagus nerve stimulation improves cortical functional topological properties and intracortical facilitation in patients with Parkinson’s disease 经皮耳廓迷走神经刺激可改善帕金森病患者的皮层功能拓扑特性和皮层内促进作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-01 DOI: 10.1038/s41531-025-00889-1

Heng Zhang, Ai-di Shan, Ya-yi Huang, Meng-xi Gao, Chen-hui Wan, Shi-yi Ye, Cai-ting Gan, Hui-min Sun, Xing-yue Cao, Yong-sheng Yuan, Ke-zhong Zhang

{"title":"Transcutaneous auricular vagus nerve stimulation improves cortical functional topological properties and intracortical facilitation in patients with Parkinson’s disease","authors":"Heng Zhang, Ai-di Shan, Ya-yi Huang, Meng-xi Gao, Chen-hui Wan, Shi-yi Ye, Cai-ting Gan, Hui-min Sun, Xing-yue Cao, Yong-sheng Yuan, Ke-zhong Zhang","doi":"10.1038/s41531-025-00889-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00889-1","url":null,"abstract":"Our study aimed to investigate the neural mechanisms of taVNS in the motor symptoms of PD, focusing on the topological properties of cortical functional networks and cortical excitability. Thirty-two PD patients underwent functional near‐infrared spectroscopy and transcranial magnetic stimulation evaluation prior to and after two-week taVNS, which were controlled by 20 healthy controls (HCs). PD patients exhibited decreased nodal efficiency (Ne) in the right M1 and increased Ne in the left pre‐motor and supplementary motor area compared with HCs. The decreased Ne in the right M1 was negatively associated with UPDRS-III scores. Interestingly, taVNS treatment improved PD motor symptoms by increasing Ne in the right M1 and enhancing intracortical facilitation (ICF, ISI 10, and 15 ms). The increased Ne and ICF (ISI 15 ms) were negatively correlated with the decreased UPDRS-III scores. taVNS could improve nodal information processing efficiency in the M1 and enhance cortical facilitation to improve PD motor disorders.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528270","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 co-culture model of T cells and midbrain organoids for investigating neurodegeneration in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-02-28 DOI: 10.1038/s41531-025-00882-8

Elizaveta Gerasimova, Amke C. Beenen, Daniil Kachkin, Martin Regensburger, Sebastian Zundler, David B. Blumenthal, Gloria Lutzny-Geier, Beate Winner, Iryna Prots

{"title":"Novel co-culture model of T cells and midbrain organoids for investigating neurodegeneration in Parkinson’s disease","authors":"Elizaveta Gerasimova, Amke C. Beenen, Daniil Kachkin, Martin Regensburger, Sebastian Zundler, David B. Blumenthal, Gloria Lutzny-Geier, Beate Winner, Iryna Prots","doi":"10.1038/s41531-025-00882-8","DOIUrl":"https://doi.org/10.1038/s41531-025-00882-8","url":null,"abstract":"Recent studies demonstrate that brain infiltration of peripheral immune cells and their interaction with brain-resident cells contribute to Parkinson’s disease (PD). However, mechanisms of T cell-brain cell communication are not fully elucidated and models allowing investigation of interaction between T cells and brain-resident cells are required. In this study, we developed a three-dimensional (3D) model composed of stem cell-derived human midbrain organoids (hMO) and peripheral blood T cells. We demonstrated that organoids consist of multiple midbrain-specific cell types, allowing to study T cell motility and interactions with midbrain tissue in a spatially organized microenvironment. We optimized co-culture conditions and demonstrated that T cells infiltrate hMO tissue, leading to neural cell loss. Our work establishes a novel 3D cell co-culture model as a promising tool to investigate the effect of the adaptive immune system on the midbrain and can be used in future studies to address these processes in the context of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"64 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518655","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

Early detection of Parkinson's disease through multiplex blood and urine biomarkers prior to clinical diagnosis.

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-02-25 DOI: 10.1038/s41531-025-00888-2

Shuo Gao, Zheng Wang, Yuanfeng Huang, Guang Yang, Yijing Wang, Yan Yi, Qiao Zhou, Xingxing Jian, Guihu Zhao, Bin Li, Linyong Xu, Kun Xia, Beisha Tang, Jinchen Li

{"title":"Early detection of Parkinson's disease through multiplex blood and urine biomarkers prior to clinical diagnosis.","authors":"Shuo Gao, Zheng Wang, Yuanfeng Huang, Guang Yang, Yijing Wang, Yan Yi, Qiao Zhou, Xingxing Jian, Guihu Zhao, Bin Li, Linyong Xu, Kun Xia, Beisha Tang, Jinchen Li","doi":"10.1038/s41531-025-00888-2","DOIUrl":"10.1038/s41531-025-00888-2","url":null,"abstract":"Blood and urine biomarkers are commonly used to diagnose and monitor chronic diseases. We initially screened 67 biomarkers, including 4 urine biomarkers and 63 blood biomarkers, and identified 13 blood biomarkers significantly associated with Parkinson's disease (PD). Among these, we discovered three novel markers demonstrating strong associations: phosphate (P = 1.81 × 10-3), AST/ALT ratio (P = 8.53 × 10-6), and immature reticulocyte fraction (IRF) (P = 3.49 × 10-20). We also substantiated eight well-studied biomarkers and elucidated the roles of two previously ambiguous biomarkers. Our analyses confirmed IGF-1 (P = 7.46 × 10-29) as a risk factor, and C-reactive protein (CRP) (P = 1.43 × 10-3) as protective against PD. Genetic analysis highlighted that IRF, CRP, and IGF-1 share significant genetic loci with PD, notably at MAPT, SETD1A, HLA-DRB1, and HLA-DQA1. Furthermore, Mendelian randomization (MR) analysis suggested potential causal associations between IGF-1, CRP, and PD. We identified several blood biomarkers that may be associated with the risk of developing PD, providing valuable insights for further exploration of PD-related biomarkers.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":"35"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493226","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

Clinical and functional evidence for the pathogenicity of the LRRK2 p.Arg1067Gln variant

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-02-23 DOI: 10.1038/s41531-025-00884-6

Shen-Yang Lim, Tzi Shin Toh, Jia Wei Hor, Jia Lun Lim, Lei Cheng Lit, Azlina Ahmad-Annuar, Yi Wen Tay, Jia Nee Foo, Ebonne Yulin Ng, Kalai Arasu Muthusamy, Norlinah Mohamed Ibrahim, Khairul Azmi Ibrahim, Louis Chew Seng Tan, Jannah Zulkefli, Anis Nadhirah Khairul Anuar, Kirsten Black, Pawel Lis, Fei Xie, Zhidong Cen, Kai Shi Lim, Katja Lohmann, Shalini Padmanabhan, Dario R. Alessi, Wei Luo, Eng King Tan, Esther Sammler, Ai Huey Tan

{"title":"Clinical and functional evidence for the pathogenicity of the LRRK2 p.Arg1067Gln variant","authors":"Shen-Yang Lim, Tzi Shin Toh, Jia Wei Hor, Jia Lun Lim, Lei Cheng Lit, Azlina Ahmad-Annuar, Yi Wen Tay, Jia Nee Foo, Ebonne Yulin Ng, Kalai Arasu Muthusamy, Norlinah Mohamed Ibrahim, Khairul Azmi Ibrahim, Louis Chew Seng Tan, Jannah Zulkefli, Anis Nadhirah Khairul Anuar, Kirsten Black, Pawel Lis, Fei Xie, Zhidong Cen, Kai Shi Lim, Katja Lohmann, Shalini Padmanabhan, Dario R. Alessi, Wei Luo, Eng King Tan, Esther Sammler, Ai Huey Tan","doi":"10.1038/s41531-025-00884-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00884-6","url":null,"abstract":"LRRK2-related Parkinson’s disease (LRRK2-PD) is the most frequent form of monogenic PD worldwide, with important therapeutic opportunities, exemplified by the advancement in LRRK2 kinase inhibition studies/trials. However, many LRRK2 variants, especially those found in underrepresented populations, remain classified as variants of uncertain significance (VUS). Leveraging on Malaysian, Singaporean, and mainland Chinese PD datasets (n = 4901), we describe 12 Chinese-ancestry patients harboring the LRRK2 p.Arg1067Gln variant, more than doubling the number of previously reported cases (total n = 23, 87% East Asian, mean age of onset: 53.9 years). We determine that this variant is enriched in East Asian PD patients compared to population controls (OR = 8.0, 95% CI: 3.0–20.9), and provide supportive data for its co-segregation with PD, albeit with incomplete penetrance. Utilizing established experimental workflows, this variant showed increased LRRK2 kinase activity, by ~2-fold compared to wildtype and higher than the p.Gly2019Ser variant. Taken together, p.Arg1067Gln should be reclassified from a VUS to pathogenic for causing LRRK2-PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"61 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473450","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

Subregion-specific associations of the basal forebrain with sleep and cognition in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-02-20 DOI: 10.1038/s41531-025-00880-w

Jung Hyun Lee, Han-Kyeol Kim, Sung Jun Ahn, Mina Park, Han Soo Yoo, Chul Hyoung Lyoo

{"title":"Subregion-specific associations of the basal forebrain with sleep and cognition in Parkinson’s disease","authors":"Jung Hyun Lee, Han-Kyeol Kim, Sung Jun Ahn, Mina Park, Han Soo Yoo, Chul Hyoung Lyoo","doi":"10.1038/s41531-025-00880-w","DOIUrl":"https://doi.org/10.1038/s41531-025-00880-w","url":null,"abstract":"To elucidate the role of basal forebrain (BF) in non-motor symptoms of Parkinson’s disease (PD), we investigated the association of sleep quality and cognition with BF volume and functional connectivity. The gray matter volume of the anterior intermediate part (Ch4ai) and the anterior lateral part (Ch4al) of the nucleus basalis Meynert were negatively associated with the PSQI global score. The posterior part of the nucleus basalis Meynert (Ch4p) volume was positively associated with visuospatial, memory, and executive functions. The PSQI global score correlated positively with functional connectivity from the Ch4al to the posterior cingulate, inferior parietal, anterior temporal, and medial prefrontal cortices, which correspond to the default mode network. Our results demonstrated that reduced volume of the anterior portion of the Ch4 and its aberrantly increased functional connectivity with the default mode network were closely related to poor overall sleep quality, while reduced volume of the posterior portion of the Ch4 was associated with decreased cognitive function in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462532","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

Motor cortex stimulation ameliorates parkinsonian locomotor deficits: effectual and mechanistic differences from subthalamic modulation

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-02-19 DOI: 10.1038/s41531-025-00879-3

Lan-Hsin Nancy Lee, Chen Yuan Ngan, Cheng-Kai Yang, Ren-Wei Wang, Hsing-Jung Lai, Chia-Hsiang Chen, Ya-Chin Yang, Chung-Chin Kuo

{"title":"Motor cortex stimulation ameliorates parkinsonian locomotor deficits: effectual and mechanistic differences from subthalamic modulation","authors":"Lan-Hsin Nancy Lee, Chen Yuan Ngan, Cheng-Kai Yang, Ren-Wei Wang, Hsing-Jung Lai, Chia-Hsiang Chen, Ya-Chin Yang, Chung-Chin Kuo","doi":"10.1038/s41531-025-00879-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00879-3","url":null,"abstract":"Subthalamic deep brain stimulation (STN DBS) has been a therapeutic choice for Parkinson’s disease (PD). We found that epidural motor cortex stimulation (MCS) with sustained positive (hyperpolarizing) currents could also consistently ameliorate the locomotor deficits in parkinsonian animals, rectifying the pathological paucity in both discharging unit varieties and movement-dependent spatiotemporal activity pattern changes in motor cortex (MC). Mechanistically, MCS hyperpolarizes both glutamatergic pyramidal neurons (PN) and GABAergic interneurons (IN) and consequently partly relieves PN from IN’s control. MC discharging units are thus enlarged with enhanced PN burst discharges against a relatively silenced background, presumably compensating for the hypoactive striatal selection to restore the MC activity changes upon movement. Behaviorally, MCS retains interim short pauses like normal locomotor behaviors, in contrast to the propensity of abnormal “restlessness” with STN DBS. Individually designed MCS, alone or in combination with STN DBS and dopaminergic therapy, may provide an optimal therapeutic approach for PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"81 3 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451625","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