NPJ Parkinson's Disease最新文献_第6页

Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice 昼夜节律紊乱会促进小鼠体内低聚α-突触核蛋白的神经毒性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-27 DOI: 10.1038/s41531-024-00798-9

Jin-Bao Zhang, Xiao-Jie Wan, Wen-Xiang Duan, Xue-Qin Dai, Dong Xia, Xiang Fu, Li-Fang Hu, Fen Wang, Chun-Feng Liu

{"title":"Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice","authors":"Jin-Bao Zhang, Xiao-Jie Wan, Wen-Xiang Duan, Xue-Qin Dai, Dong Xia, Xiang Fu, Li-Fang Hu, Fen Wang, Chun-Feng Liu","doi":"10.1038/s41531-024-00798-9","DOIUrl":"https://doi.org/10.1038/s41531-024-00798-9","url":null,"abstract":"Circadian disruption often arises prior to the onset of typical motor deficits in patients with Parkinson’s disease (PD). It remains unclear whether such a prevalent non-motor manifestation would contribute to the progression of PD. Diffusible oligomeric alpha-synuclein (O-αSyn) is perceived as the most toxic and rapid-transmitted species in the early stages of PD. Exploring the factors that influence the spread and toxicity of O-αSyn should be helpful for developing effective interventions for the disease. The aim of this study was to explore the effects of circadian disruption on PD pathology and parkinsonism-like behaviors in a novel mouse model induced by O-αSyn. We discovered that O-αSyn could enter the brain rapidly following intranasal administration, resulting in the formation of nitrated-αSyn pathology and non-motor symptoms of the mice. Meanwhile, circadian disruption exacerbated the burden of nitrated-αSyn pathology and accelerated the loss of dopaminergic neurons in O-αSyn-treated mice. Subsequent experiments demonstrated that circadian disruption might act via promoting nitrative stress and neuroinflammation. These findings could highlight the circadian rhythms as a potential diagnostic and therapeutic target in early-stage PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"66 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328865","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

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts 神经元α-突触核蛋白病综合分期系统在 PPMI、PASADENA 和 SPARK 基线队列中的表现

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-27 DOI: 10.1038/s41531-024-00789-w

Tien Dam, Gennaro Pagano, Michael C. Brumm, Caroline Gochanour, Kathleen L. Poston, Daniel Weintraub, Lana M. Chahine, Christopher Coffey, Caroline M. Tanner, Catherine M. Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter DiBiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J. Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek

{"title":"Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts","authors":"Tien Dam, Gennaro Pagano, Michael C. Brumm, Caroline Gochanour, Kathleen L. Poston, Daniel Weintraub, Lana M. Chahine, Christopher Coffey, Caroline M. Tanner, Catherine M. Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter DiBiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J. Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek","doi":"10.1038/s41531-024-00789-w","DOIUrl":"https://doi.org/10.1038/s41531-024-00789-w","url":null,"abstract":"The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"5 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325344","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

Intravenous arachnoid granulation hypertrophy in patients with Parkinson disease. 帕金森病患者静脉内蛛网膜肉芽肥大。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-20 DOI: 10.1038/s41531-024-00796-x

Melanie Leguizamon,Colin D McKnight,Tristan Ponzo,Jason Elenberger,Jarrod J Eisma,Alexander K Song,Paula Trujillo,Ciaran M Considine,Manus J Donahue,Daniel O Claassen,Kilian Hett

{"title":"Intravenous arachnoid granulation hypertrophy in patients with Parkinson disease.","authors":"Melanie Leguizamon,Colin D McKnight,Tristan Ponzo,Jason Elenberger,Jarrod J Eisma,Alexander K Song,Paula Trujillo,Ciaran M Considine,Manus J Donahue,Daniel O Claassen,Kilian Hett","doi":"10.1038/s41531-024-00796-x","DOIUrl":"https://doi.org/10.1038/s41531-024-00796-x","url":null,"abstract":"Intravenous arachnoid granulations (AGs) are protrusions of the arachnoid membrane into the venous lumen and function as contributors to the cerebrospinal fluid (CSF) flow circuit. Patients with Parkinson disease (PD) often present with accumulation of alpha synuclein. Previous works have provided evidence for neurofluid circulation dysfunction in neurodegenerative diseases associated with changes in CSF egress, which may have implications regarding AG morphology. The present study aims to investigate group differences in AG volumetrics between healthy and PD participants, as well as relationships between AG characteristics and clinical assessments. Generalized linear models revealed significant increases in AG volumetrics and number in PD compared to healthy controls. Partial Spearman-rank correlation analyses demonstrated significant relationships between AG metrics and motor and cognitive assessments. Finally, AG volumetrics were positively correlated with objective actigraphy measures of sleep dysfunction, but not self-report sleep symptoms.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"41 1","pages":"177"},"PeriodicalIF":8.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275332","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

Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial 帕金森病个性化治疗自适应 DBS 算法（ADAPT-PD）临床试验的传感数据和方法论

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-17 DOI: 10.1038/s41531-024-00772-5

Scott Stanslaski, Rebekah L. S. Summers, Lisa Tonder, Ye Tan, Michelle Case, Robert S. Raike, Nathan Morelli, Todd M. Herrington, Martijn Beudel, Jill L. Ostrem, Simon Little, Leonardo Almeida, Adolfo Ramirez-Zamora, Alfonso Fasano, Travis Hassell, Kyle T. Mitchell, Elena Moro, Michal Gostkowski, Nagaraja Sarangmat, Helen Bronte-Stewart

{"title":"Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial","authors":"Scott Stanslaski, Rebekah L. S. Summers, Lisa Tonder, Ye Tan, Michelle Case, Robert S. Raike, Nathan Morelli, Todd M. Herrington, Martijn Beudel, Jill L. Ostrem, Simon Little, Leonardo Almeida, Adolfo Ramirez-Zamora, Alfonso Fasano, Travis Hassell, Kyle T. Mitchell, Elena Moro, Michal Gostkowski, Nagaraja Sarangmat, Helen Bronte-Stewart","doi":"10.1038/s41531-024-00772-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00772-5","url":null,"abstract":"Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"6 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235242","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

Increased sighing during sleep as a marker of multiple system atrophy 睡眠中叹息声增多是多系统萎缩的标志

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-16 DOI: 10.1038/s41531-024-00765-4

Estefania Vargas Gonzalez, Zhongmei Yang, Pauline Dodet, Smaranda Leu-Semenescu, Cécile Londner, Maxime Patout, Christian Straus, Thomas Similowski, David Grabli, Marie Vidailhet, Isabelle Arnulf

{"title":"Increased sighing during sleep as a marker of multiple system atrophy","authors":"Estefania Vargas Gonzalez, Zhongmei Yang, Pauline Dodet, Smaranda Leu-Semenescu, Cécile Londner, Maxime Patout, Christian Straus, Thomas Similowski, David Grabli, Marie Vidailhet, Isabelle Arnulf","doi":"10.1038/s41531-024-00765-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00765-4","url":null,"abstract":"Parkinson’s disease (PD) and multiple system atrophy (MSA) can be preceded by isolated REM sleep behavior disorder (iRBD). As excessive sighing during wakefulness is a red flag for MSA in individuals with parkinsonism, we measured sighing during slow wave sleep (N3) and REM sleep as potential biomarkers in 73 participants with MSA, 111 with iRBD, 257 with PD, and 115 controls. The number of sighs/hour of N3 (index) was higher in the MSA group than in the other groups. Sighs were rarer in REM sleep than in N3 sleep. A sigh index greater than 3.4/h of N3 was 95% sensitive in discriminating participants with MSA from controls, and a sigh index greater than 0.8 sigh/h of REM sleep was 87% specific in discriminating participants with MSA from controls. MSA participants with (vs. without) sigh were younger, had a lower apnea-hypopnea index (but no more stridor), and had no other difference in motor, autonomic, cognitive, and sensory symptoms. The sigh index could be used for screening for MSA in the millions of middle-aged persons who receive polysomnography for other purposes. Whether sighing in iRBD predicts preferential conversion towards MSA should be measured in a longitudinal study.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"55 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234436","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

Clinico-physiological correlates of Parkinson’s disease from multi-resolution basal ganglia recordings 通过多分辨率基底神经节记录了解帕金森病的临床生理学相关性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-12 DOI: 10.1038/s41531-024-00773-4

Srdjan Sumarac, Jinyoung Youn, Conor Fearon, Luka Zivkovic, Prerana Keerthi, Oliver Flouty, Milos Popovic, Mojgan Hodaie, Suneil Kalia, Andres Lozano, William Hutchison, Alfonso Fasano, Luka Milosevic

{"title":"Clinico-physiological correlates of Parkinson’s disease from multi-resolution basal ganglia recordings","authors":"Srdjan Sumarac, Jinyoung Youn, Conor Fearon, Luka Zivkovic, Prerana Keerthi, Oliver Flouty, Milos Popovic, Mojgan Hodaie, Suneil Kalia, Andres Lozano, William Hutchison, Alfonso Fasano, Luka Milosevic","doi":"10.1038/s41531-024-00773-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00773-4","url":null,"abstract":"Parkinson’s disease (PD) has been associated with pathological neural activity within the basal ganglia. Herein, we analyzed resting-state single-neuron and local field potential (LFP) activities from people with PD who underwent awake deep brain stimulation surgery of the subthalamic nucleus (STN; n = 125) or globus pallidus internus (GPi; n = 44), and correlated rate-based and oscillatory features with UPDRSIII off-medication subscores. Rate-based single-neuron features did not correlate with PD symptoms. STN single-neuron and LFP low-beta (12–21 Hz) power and burst dynamics showed modest correlations with bradykinesia and rigidity severity, while STN spiketrain theta (4–8 Hz) power correlated modestly with tremor severity. GPi low- and high-beta (21–30 Hz) power and burst dynamics correlated moderately with bradykinesia and axial symptom severity. These findings suggest that elevated single-neuron and LFP oscillations may be linked to symptoms, though modest correlations imply that the pathophysiology of PD may extend beyond resting-state beta oscillations.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"149 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170753","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

Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease 直立性低血压：帕金森病患者 "身体优先 "亚型的临床标记

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-11 DOI: 10.1038/s41531-024-00787-y

Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan

{"title":"Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease","authors":"Shanshan Mei, Xue Wang, Wei Mao, Yue Liu, Zichen Tian, Chao Han, Piu Chan","doi":"10.1038/s41531-024-00787-y","DOIUrl":"https://doi.org/10.1038/s41531-024-00787-y","url":null,"abstract":"Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"9 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166279","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

GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate 神经变性过程中的 GPR37 处理：帕金森病进展速度的潜在标志物

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-10 DOI: 10.1038/s41531-024-00788-x

Josep Argerich, Leonardo D. Garma, Marc López-Cano, Paula Álvarez-Montoya, Laura Gómez-Acero, Víctor Fernández-Dueñas, Ana B. Muñoz-Manchado, Ester Aso, Adam Boxer, Pol Andres-Benito, Per Svenningsson, Francisco Ciruela

{"title":"GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate","authors":"Josep Argerich, Leonardo D. Garma, Marc López-Cano, Paula Álvarez-Montoya, Laura Gómez-Acero, Víctor Fernández-Dueñas, Ana B. Muñoz-Manchado, Ester Aso, Adam Boxer, Pol Andres-Benito, Per Svenningsson, Francisco Ciruela","doi":"10.1038/s41531-024-00788-x","DOIUrl":"https://doi.org/10.1038/s41531-024-00788-x","url":null,"abstract":"The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"151 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166244","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

The value of PET/CT in the diagnosis and differential diagnosis of Parkinson’s disease: a dual-tracer study PET/CT 在帕金森病诊断和鉴别诊断中的价值：一项双示踪剂研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-10 DOI: 10.1038/s41531-024-00786-z

Xiaoxiao Du, Hongguang Zhao, Yinghua Li, Yuyin Dai, Lulu Gao, Yi Li, Kangli Fan, Zhihui Sun, Ying Zhang

{"title":"The value of PET/CT in the diagnosis and differential diagnosis of Parkinson’s disease: a dual-tracer study","authors":"Xiaoxiao Du, Hongguang Zhao, Yinghua Li, Yuyin Dai, Lulu Gao, Yi Li, Kangli Fan, Zhihui Sun, Ying Zhang","doi":"10.1038/s41531-024-00786-z","DOIUrl":"https://doi.org/10.1038/s41531-024-00786-z","url":null,"abstract":"Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson’s disease (PD). This study aimed to evaluate the performance of PET/CT with 11C-2β-Carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. 11C-CFT and 18F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of 11C-CFT and 18F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on 11C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in 11C-CFT uptake. The areas under the curve (AUCs) for 11C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On 18F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that 11C-CFT and 18F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160612","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

Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity α-突触核蛋白诱导的黑质变性和普拉克索治疗会破坏前额纹状体的可塑性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-09-09 DOI: 10.1038/s41531-024-00781-4

Sarah Chevalier, Mélina Decourt, Maureen Francheteau, François Nicol, Anaïs Balbous, Pierre-Olivier Fernagut, Marianne Benoit-Marand

{"title":"Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity","authors":"Sarah Chevalier, Mélina Decourt, Maureen Francheteau, François Nicol, Anaïs Balbous, Pierre-Olivier Fernagut, Marianne Benoit-Marand","doi":"10.1038/s41531-024-00781-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00781-4","url":null,"abstract":"Parkinson’s disease is characterized by the degeneration of substantia nigra pars compacta (SNc) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular and molecular adaptations following neurodegeneration or dopamine replacement therapy (DRT) have been described in motor networks but little is known regarding associative basal ganglia loops. This study investigated the contributions of nigrostriatal degeneration and pramipexole (PPX) on neuronal activity in the orbitofrontal cortex (OFC), frontostriatal plasticity, and markers of synaptic plasticity. Bilateral nigrostriatal degeneration was induced by viral-mediated expression of human mutated alpha-synuclein in the SNc. Juxtacellular recordings were performed in anesthetized rats to evaluate neuronal activity in the OFC. Recordings in the dorsomedial striatum (DMS) were performed, and spike probability in response to OFC stimulation was measured before and after high-frequency stimulation (HFS). Post-mortem analysis included stereological assessment of nigral neurodegeneration, BDNF and TrkB protein levels. Nigrostriatal neurodegeneration led to altered firing patterns of OFC neurons that were restored by PPX. HFS of the OFC led to an increased spike probability in the DMS, while dopaminergic loss had the opposite effect. PPX led to a decreased spike probability following HFS in control rats and failed to counteract the effect of dopaminergic neurodegeneration. These alterations were associated with decreased levels of BDNF and TrkB in the DMS. This study demonstrates that nigral dopaminergic loss and PPX both contribute to alter frontostriatal transmission, precluding adequate information processing in associative basal ganglia loops as a gateway for the development of non-motor symptoms or non-motor side effects of DRT.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"48 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158952","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}

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