NPJ Parkinson's Disease最新文献

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Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor 针对尾椎内侧的深部脑刺激治疗本质性震颤
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-22 DOI: 10.1038/s41531-024-00833-9
Rasmus Stenmark Persson, Yulia Blomstedt, Anders Fytagoridis, Marwan Hariz, Patric Blomstedt
{"title":"Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor","authors":"Rasmus Stenmark Persson, Yulia Blomstedt, Anders Fytagoridis, Marwan Hariz, Patric Blomstedt","doi":"10.1038/s41531-024-00833-9","DOIUrl":"https://doi.org/10.1038/s41531-024-00833-9","url":null,"abstract":"<p>To compare awake and asleep deep brain stimulation (DBS) surgery for Essential Tremor (ET), we conducted this retrospective cohort study of patients consecutively operated with DBS targeting the caudal Zona incerta (cZi). 37 underwent surgery awake and 55 asleep. Tremor before surgery and on/off stimulation one year after surgery were evaluated using the Essential Tremor Rating Scale (ETRS). Procedural time, electrode localization, stimulation parameters and adverse events were noted and compared. ETRS scores were similar at baseline between the groups except for contralateral arm tremor, which was slightly worse in the awake group. Total ETRS, contralateral arm tremor and activities of daily living scores showed no significant difference between the groups on-stimulation at one-year follow-up. Compared to the awake group, the asleep group had shorter procedural time and lower stimulation parameters. There were no intracranial haemorrhages nor surgery site-infections. Both groups showed a good improvement of tremor at one-year follow-up. Image-guided DBS surgery targeting the cZi enables safe and efficient asleep surgery for ET.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"36 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684149","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
Accelerating Parkinson’s Disease drug development with federated learning approaches 利用联合学习方法加速帕金森病药物开发
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-21 DOI: 10.1038/s41531-024-00837-5
Amit Khanna, Jamie Adams, Chrystalina Antoniades, Bastiaan R. Bloem, Camille Carroll, Jesse Cedarbaum, Joshua Cosman, David T. Dexter, Marissa F. Dockendorf, Jeremy Edgerton, Laura Gaetano, Erkuden Goikoetxea, Derek Hill, Fay Horak, Elena S. Izmailova, Tairmae Kangarloo, Dina Katabi, Catherine Kopil, Michael Lindemann, Jennifer Mammen, Kenneth Marek, Kevin McFarthing, Anat Mirelman, Martijn Muller, Gennaro Pagano, M. Judith Peterschmitt, Jie Ren, Lynn Rochester, Sakshi Sardar, Andrew Siderowf, Tanya Simuni, Diane Stephenson, Christine Swanson-Fischer, John A. Wagner, Graham B. Jones
{"title":"Accelerating Parkinson’s Disease drug development with federated learning approaches","authors":"Amit Khanna, Jamie Adams, Chrystalina Antoniades, Bastiaan R. Bloem, Camille Carroll, Jesse Cedarbaum, Joshua Cosman, David T. Dexter, Marissa F. Dockendorf, Jeremy Edgerton, Laura Gaetano, Erkuden Goikoetxea, Derek Hill, Fay Horak, Elena S. Izmailova, Tairmae Kangarloo, Dina Katabi, Catherine Kopil, Michael Lindemann, Jennifer Mammen, Kenneth Marek, Kevin McFarthing, Anat Mirelman, Martijn Muller, Gennaro Pagano, M. Judith Peterschmitt, Jie Ren, Lynn Rochester, Sakshi Sardar, Andrew Siderowf, Tanya Simuni, Diane Stephenson, Christine Swanson-Fischer, John A. Wagner, Graham B. Jones","doi":"10.1038/s41531-024-00837-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00837-5","url":null,"abstract":"<p>Parkinson’s Disease is a progressive neurodegenerative disorder afflicting almost 12 million people. Increased understanding of its complex and heterogenous disease pathology, etiology and symptom manifestations has resulted in the need to design, capture and interrogate substantial clinical datasets. Herein we advocate how advances in the deployment of artificial intelligence models for Federated Data Analysis and Federated Learning can help spearhead coordinated and sustainable approaches to address this grand challenge.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"73 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678609","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
Push-pull effects of basal ganglia network in Parkinson’s disease inferred by functional MRI 通过功能磁共振成像推断帕金森病基底神经节网络的推拉效应
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-20 DOI: 10.1038/s41531-024-00835-7
Yuxin Wang, Zhiqi Jiang, Chunguang Chu, Zhen Zhang, Jiang Wang, Dianyou Li, Naying He, Chris Fietkiewicz, Changsong Zhou, Marcus Kaiser, Xuze Bai, Chencheng Zhang, Chen Liu
{"title":"Push-pull effects of basal ganglia network in Parkinson’s disease inferred by functional MRI","authors":"Yuxin Wang, Zhiqi Jiang, Chunguang Chu, Zhen Zhang, Jiang Wang, Dianyou Li, Naying He, Chris Fietkiewicz, Changsong Zhou, Marcus Kaiser, Xuze Bai, Chencheng Zhang, Chen Liu","doi":"10.1038/s41531-024-00835-7","DOIUrl":"https://doi.org/10.1038/s41531-024-00835-7","url":null,"abstract":"<p>Deep brain stimulation (DBS) can ameliorate motor symptoms in Parkinson’s disease (PD), but its mechanism remains unclear. This work constructs a multi-scale brain model using the fMRI data from 27 PD patients with subthalamic DBS and 30 healthy controls. The model fits microscopic coupling parameters in the cortico-basal ganglia-thalamic neural loop to match individual connectivity, finding the “push-pull” effect of basal ganglia network. Specifically, increased GABAergic projection into the thalamus from basal ganglia worsens rigidity, while reduced GABAergic projection within the cortex exacerbates bradykinesia, suggesting that the dopamine deficiency induces the chain coupling variations to “push” the network to an abnormal state. Conversely, DBS can alleviate rigidity by enhancing GABAergic projections within the basal ganglia, and improve bradykinesia by reducing cortical projections to basal ganglia, exhibiting that DBS “pulls” the network to a healthy state. This work combines the microscopic and macroscopic neural information for understanding PD and its treatment.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"23 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673892","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
A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease. 皮层下形状作为帕金森病临床分期标志的全球研究。
IF 6.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-19 DOI: 10.1038/s41531-024-00825-9
Max A Laansma, Yuji Zhao, Eva M van Heese, Joanna K Bright, Conor Owens-Walton, Sarah Al-Bachari, Tim J Anderson, Francesca Assogna, Tim D van Balkom, Henk W Berendse, Fernando Cendes, John C Dalrymple-Alford, Ines Debove, Michiel F Dirkx, Jason Druzgal, Hedley C A Emsley, Jean-Paul Fouche, Gaëtan Garraux, Rachel P Guimarães, Rick C Helmich, Michele Hu, Odile A van den Heuvel, Dmitry Isaev, Ho-Bin Kim, Johannes C Klein, Christine Lochner, Corey T McMillan, Tracy R Melzer, Benjamin Newman, Laura M Parkes, Clelia Pellicano, Fabrizio Piras, Toni L Pitcher, Kathleen L Poston, Mario Rango, Leticia F Ribeiro, Cristiane S Rocha, Christian Rummel, Lucas S R Santos, Reinhold Schmidt, Petra Schwingenschuh, Letizia Squarcina, Dan J Stein, Daniela Vecchio, Chris Vriend, Jiunjie Wang, Daniel Weintraub, Roland Wiest, Clarissa L Yasuda, Neda Jahanshad, Paul M Thompson, Ysbrand D van der Werf, Boris A Gutman
{"title":"A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.","authors":"Max A Laansma, Yuji Zhao, Eva M van Heese, Joanna K Bright, Conor Owens-Walton, Sarah Al-Bachari, Tim J Anderson, Francesca Assogna, Tim D van Balkom, Henk W Berendse, Fernando Cendes, John C Dalrymple-Alford, Ines Debove, Michiel F Dirkx, Jason Druzgal, Hedley C A Emsley, Jean-Paul Fouche, Gaëtan Garraux, Rachel P Guimarães, Rick C Helmich, Michele Hu, Odile A van den Heuvel, Dmitry Isaev, Ho-Bin Kim, Johannes C Klein, Christine Lochner, Corey T McMillan, Tracy R Melzer, Benjamin Newman, Laura M Parkes, Clelia Pellicano, Fabrizio Piras, Toni L Pitcher, Kathleen L Poston, Mario Rango, Leticia F Ribeiro, Cristiane S Rocha, Christian Rummel, Lucas S R Santos, Reinhold Schmidt, Petra Schwingenschuh, Letizia Squarcina, Dan J Stein, Daniela Vecchio, Chris Vriend, Jiunjie Wang, Daniel Weintraub, Roland Wiest, Clarissa L Yasuda, Neda Jahanshad, Paul M Thompson, Ysbrand D van der Werf, Boris A Gutman","doi":"10.1038/s41531-024-00825-9","DOIUrl":"10.1038/s41531-024-00825-9","url":null,"abstract":"<p><p>Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4-5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"223"},"PeriodicalIF":6.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668565","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
Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease 尾状核多巴胺能末梢的相对稀缺是帕金森病静止性震颤的一个特征
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-18 DOI: 10.1038/s41531-024-00818-8
Marcelo D. Mendonça, Pedro C. Ferreira, Francisco Oliveira, Raquel Barbosa, Bruna Meira, Durval C. Costa, Albino J. Oliveira-Maia, Joaquim Alves da Silva
{"title":"Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease","authors":"Marcelo D. Mendonça, Pedro C. Ferreira, Francisco Oliveira, Raquel Barbosa, Bruna Meira, Durval C. Costa, Albino J. Oliveira-Maia, Joaquim Alves da Silva","doi":"10.1038/s41531-024-00818-8","DOIUrl":"https://doi.org/10.1038/s41531-024-00818-8","url":null,"abstract":"<p>Resting tremor (RT) is a Parkinson’s disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate binding ratio (CBR), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4–6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group. In silico modelling uncovered that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in several datasets, supporting a spurious origin for ipsilateral correlations between CBR and RT. These results suggest that caudate dopaminergic terminals integrity is a feature of RT with potential pathophysiological implications.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"76 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665363","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
Circulating blood circular RNA in Parkinson’s Disease; from involvement in pathology to diagnostic tools in at-risk individuals 帕金森病中的循环血液环状 RNA;从病理参与到高危人群的诊断工具
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-18 DOI: 10.1038/s41531-024-00839-3
Aleksandra Beric, Yichen Sun, Santiago Sanchez, Charissa Martin, Tyler Powell, Ravindra Kumar, Jose Adrian Pardo, Gauri Darekar, Jessie Sanford, Devin Dikec, Bridget Phillips, Juan A. Botia, Carlos Cruchaga, Laura Ibanez
{"title":"Circulating blood circular RNA in Parkinson’s Disease; from involvement in pathology to diagnostic tools in at-risk individuals","authors":"Aleksandra Beric, Yichen Sun, Santiago Sanchez, Charissa Martin, Tyler Powell, Ravindra Kumar, Jose Adrian Pardo, Gauri Darekar, Jessie Sanford, Devin Dikec, Bridget Phillips, Juan A. Botia, Carlos Cruchaga, Laura Ibanez","doi":"10.1038/s41531-024-00839-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00839-3","url":null,"abstract":"<p>To identify circRNAs associated with Parkinson’s disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (<i>N</i> = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry. The 192 circRNAs were leveraged to distinguish between PD and healthy participants with a ROC AUC of 0.797. Further, 71 circRNAs were sufficient to distinguish between genetic PD (AUC<sub>71</sub> = 0.954) and, at-risk participants (AUC<sub>71</sub> = 0.929) and healthy controls, supporting that circRNAs have the potential to aid the diagnosis of PD. Finally, we identified five circRNAs highly correlated with symptom severity. Overall, we demonstrated that circRNAs play an important role in PD and can be clinically relevant to improve diagnostic and monitoring.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"8 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665365","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
Occipital hypoperfusion and motor reserve in Parkinson’s disease: an early-phase 18F-FP-CIT PET study 帕金森病的枕叶低灌注和运动储备:早期 18F-FP-CIT PET 研究
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-17 DOI: 10.1038/s41531-024-00834-8
Yeo Jun Yoon, Su Hong Kim, Seong Ho Jeong, Chan Wook Park, Hye Sun Lee, Phil Hyu Lee, Yun Joong Kim, Young H. Sohn, Yong Jeong, Seok Jong Chung
{"title":"Occipital hypoperfusion and motor reserve in Parkinson’s disease: an early-phase 18F-FP-CIT PET study","authors":"Yeo Jun Yoon, Su Hong Kim, Seong Ho Jeong, Chan Wook Park, Hye Sun Lee, Phil Hyu Lee, Yun Joong Kim, Young H. Sohn, Yong Jeong, Seok Jong Chung","doi":"10.1038/s41531-024-00834-8","DOIUrl":"https://doi.org/10.1038/s41531-024-00834-8","url":null,"abstract":"<p>Individual variability exists in parkinsonian motor symptoms despite a similar degree of nigrostriatal dopamine depletion in Parkinson’s disease (PD), called motor reserve. We enrolled 397 patients newly diagnosed with PD who underwent dual-phase <sup>18</sup>F-FP-CIT PET upon initial assessment. Individual motor reserve was estimated based on initial parkinsonian motor symptoms and striatal dopamine transporter availability using a residual model. Patients with low motor reserve (the lowest quartile group, <i>n</i> = 100) exhibited decreased uptake in the occipital region compared to those with high motor reserve (the highest quartile group, <i>n</i> = 100) on early-phase <sup>18</sup>F-FP-CIT PET images. Patients with high motor reserve had a lower risk of conversion to dementia than the those with low motor reserve, whereas the effect of PD groups on the risk of dementia conversion was not mediated by occipital hypoperfusion. These findings suggest that cerebral hypoperfusion in the occipital region is associated with low motor reserve in patients with PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"34 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645851","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
Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons 大麻素对血管紧张素 II 诱导的纹状体神经元钙信号转导的调控
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-15 DOI: 10.1038/s41531-024-00827-7
Rafael Rivas-Santisteban, Ana Muñoz, Jaume Lillo, Iu Raïch, Ana I. Rodríguez-Pérez, Gemma Navarro, José L. Labandeira-García, Rafael Franco
{"title":"Cannabinoid regulation of angiotensin II-induced calcium signaling in striatal neurons","authors":"Rafael Rivas-Santisteban, Ana Muñoz, Jaume Lillo, Iu Raïch, Ana I. Rodríguez-Pérez, Gemma Navarro, José L. Labandeira-García, Rafael Franco","doi":"10.1038/s41531-024-00827-7","DOIUrl":"https://doi.org/10.1038/s41531-024-00827-7","url":null,"abstract":"<p>Calcium ion (Ca<sup>2+</sup>) homeostasis is crucial for neuron function and neurotransmission. This study focused on the actions mediated by the CB<sub>1</sub> receptor (CB<sub>1</sub>R), the most abundant G protein-coupled receptor (GPCR) in central nervous system (CNS) neurons, over by the AT<sub>1</sub>R, which is one of the few G protein-coupled CNS receptors able to regulate cytoplasmic Ca<sup>2+</sup> levels. A functional interaction suggesting a direct association between these receptors was detected. AT<sub>1</sub>-CB<sub>1</sub> receptor heteromers (AT<sub>1</sub>CB<sub>1</sub>Hets) were identified in HEK-293T cells by bioluminescence resonance energy transfer (BRET<sup>2</sup>). Functional interactions within the AT<sub>1</sub>-CB<sub>1</sub> complex and their potential relevance in Parkinson’s disease (PD) were assessed. In situ proximity ligation assays (PLA) identified AT<sub>1</sub>CB<sub>1</sub>Hets in neurons, in which an important finding was that Ca<sup>2+</sup> level increase upon AT<sub>1</sub>R activation was reduced in the presence of cannabinoids acting on CB<sub>1</sub>Rs. AT<sub>1</sub>CB<sub>1</sub>Het expression was quantified in samples from the 6-hydroxydopamine (6-OHDA) hemilesioned rat model of PD in which a lower expression of AT<sub>1</sub>CB<sub>1</sub>Hets was observed in striatal neurons from lesioned animals (versus non-lesioned). AT<sub>1</sub>CB<sub>1</sub>Het expression changed depending on both the lesion and the consequences of levodopa administration, i.e., dyskinesias versus lack of involuntary movements. A partial recovery in AT<sub>1</sub>CB<sub>1</sub>Het expression was detected in lesioned animals that developed levodopa-induced dyskinesias. These findings support the existence of a compensatory mechanism mediated by AT<sub>1</sub>CB<sub>1</sub>Hets that modulates susceptibility to levodopa-induced dyskinesias in PD. Therefore, cannabinoids may be useful in reducing calcium dyshomeostasis in dyskinesia.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637183","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
Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson's disease. 外周免疫细胞丰度差异将血液线粒体 DNA 拷贝数与帕金森病联系起来。
IF 6.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-14 DOI: 10.1038/s41531-024-00831-x
Longfei Wang, Jiru Han, Liam G Fearnley, Michael Milton, Haloom Rafehi, Joshua Reid, Zachary F Gerring, Shashank Masaldan, Tali Lang, Terence P Speed, Melanie Bahlo
{"title":"Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson's disease.","authors":"Longfei Wang, Jiru Han, Liam G Fearnley, Michael Milton, Haloom Rafehi, Joshua Reid, Zachary F Gerring, Shashank Masaldan, Tali Lang, Terence P Speed, Melanie Bahlo","doi":"10.1038/s41531-024-00831-x","DOIUrl":"10.1038/s41531-024-00831-x","url":null,"abstract":"<p><p>Mitochondrial dysfunction plays an important role in Parkinson's disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson's Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. We estimated blood cell composition using complete blood cell profile when available or RNA-sequencing data as a surrogate. After adjusting for blood cell composition, the associations between mtDNA-CN and PD risk and clinical symptoms became non-significant. Bidirectional Mendelian randomization analysis also found no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Hence peripheral inflammatory immune responses rather than mitochondrial dysfunction underpin these previously identified associations in PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"219"},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625263","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
Multimodal neuroimaging-based prediction of Parkinson’s disease with mild cognitive impairment using machine learning technique 利用机器学习技术,基于多模态神经影像预测帕金森病伴轻度认知障碍
IF 8.7 1区 医学
NPJ Parkinson's Disease Pub Date : 2024-11-11 DOI: 10.1038/s41531-024-00828-6
Yongyun Zhu, Fang Wang, Pingping Ning, Yangfan Zhu, Lingfeng Zhang, Kelu Li, Bin Liu, Hui Ren, Zhong Xu, Ailan Pang, Xinglong Yang
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