NPJ Parkinson's Disease最新文献_第7页

An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ 体外和原位研究抗淀粉样蛋白化合物作用机制的方法

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-10 DOI: 10.1038/s41531-025-00966-5

P. Stalder, T. Serdiuk, D. Ghosh, Y. Fleischmann, N. Ait-Bouziad, J.-P. Quast, L. Malinovska, A. Ouared, A. Davranche, W. Haenseler, C. Boudou, E. Tsika, J. Stöhr, R. Melki, R. Riek, N. de Souza, P. Picotti

{"title":"An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ","authors":"P. Stalder, T. Serdiuk, D. Ghosh, Y. Fleischmann, N. Ait-Bouziad, J.-P. Quast, L. Malinovska, A. Ouared, A. Davranche, W. Haenseler, C. Boudou, E. Tsika, J. Stöhr, R. Melki, R. Riek, N. de Souza, P. Picotti","doi":"10.1038/s41531-025-00966-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00966-5","url":null,"abstract":"Amyloid aggregation is associated with neurodegenerative disease and its modulation is a focus of drug development. We developed a chemical proteomics pipeline to probe the mechanism of action of anti-amyloidogenic compounds. Our approach identifies putative interaction sites with high resolution, can probe compound interactions with specific target conformations and directly in cell and brain extracts, and identifies off-targets. We analysed interactions of six anti-amyloidogenic compounds and the amyloid binder Thioflavin T with different conformations of the Parkinson’s disease protein α-Synuclein and tested specific compounds in cell or brain lysates. AC Immune compound 2 interacted with α-Synuclein in vitro, in intact neurons and in neuronal lysates, reduced neuronal α-Synuclein levels in a seeded model, and had protective effects. EGCG, Baicalein, ThT and doxycycline interacted with α-Synuclein in vitro but not substantially in cell lysates, with many additional putative targets, underscoring the importance of testing compounds in situ. Our pipeline will enable screening of compounds against any amyloidogenic proteins in cell and patient brain extracts and mechanistic studies of compound action.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"117 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930959","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 zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson’s disease acmsd缺乏症的斑马鱼模型不支持acmsd在帕金森病中的突出作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-09 DOI: 10.1038/s41531-025-00940-1

Emma Fargher, Marcus Keatinge, Oluwaseyi Pearce, Petteri Piepponen, Pertti Panula, Fredericus J. M. van Eeden, Ryan B. MacDonald, Oliver Bandmann

{"title":"A zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson’s disease","authors":"Emma Fargher, Marcus Keatinge, Oluwaseyi Pearce, Petteri Piepponen, Pertti Panula, Fredericus J. M. van Eeden, Ryan B. MacDonald, Oliver Bandmann","doi":"10.1038/s41531-025-00940-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00940-1","url":null,"abstract":"Single nucleotide polymorphisms adjacent to the α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) gene have been associated with Parkinson’s disease (PD) in genome-wide association studies (GWAS). However, its biological validation as a PD risk gene has been hampered by the lack of available models. Using CRISPR/Cas9, we generated a zebrafish model of acmsd deficiency with marked increase in quinolinic acid. Despite this, acmsd-/- zebrafish were viable, fertile, morphologically normal and demonstrated no abnormalities in spontaneous movement. In contrast to the postulated pro-immune pathomechanism linking ACMSD to PD, microglial cells and expression of the proinflammatory cytokines cxcl8, il-1β, and mmp9 were similar between acmsd-/- and controls. The number of ascending dopaminergic neurons, and their susceptibility to MPP+, was also indistinguishable. An upregulation of kynurenine aminotransferase activity was identified in acmsd-/- zebrafish which may explain the absence of neurodegenerative phenotypes. Our study highlights the importance of biological validation for putative GWAS hits in suitable model systems.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"108 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927270","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

Data-driven characterization of distinct cognitive subtypes in Parkinson’s disease dementia 帕金森病痴呆中不同认知亚型的数据驱动特征

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-09 DOI: 10.1038/s41531-025-00970-9

Miguel A. Labrador-Espinosa, Jesús Silva-Rodríguez, Pablo Mir, Michel J. Grothe

{"title":"Data-driven characterization of distinct cognitive subtypes in Parkinson’s disease dementia","authors":"Miguel A. Labrador-Espinosa, Jesús Silva-Rodríguez, Pablo Mir, Michel J. Grothe","doi":"10.1038/s41531-025-00970-9","DOIUrl":"https://doi.org/10.1038/s41531-025-00970-9","url":null,"abstract":"Individual cognitive profiles of patients with Parkinson’s disease dementia (PDD) are highly heterogeneous, suggesting possible biological subtypes. We studied 75 PD patients who developed dementia in the course of the Parkinson’s Progression Markers Initiative study to investigate data-driven evidence for the existence of distinct cognitive subtypes of PDD. Using Ward’s hierarchical clustering on neuropsychological test data, we identified two distinct cognitive subtypes. Despite similar dementia severity (MoCA: 20.6 vs 20.0), cluster-A exhibited more pronounced memory deficits (n = 50), whereas cluster-B showed greater visuospatial impairments (n = 25). The subtypes did not differ in demographic, motor, or MRI-based neurodegeneration measures. However, the visuospatial-predominant cluster-B had a higher prevalence of GBA mutations (p = 0.003) and hallucinations (p = 0.009). No differences were found in APOE-ε4 prevalence or cerebrospinal fluid biomarkers of Alzheimer’s pathology. These findings reveal distinct memory-predominant and visuospatial-predominant PDD subtypes, which associate with different clinical and genetic features but are independent of comorbid Alzheimer’s pathology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"50 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930980","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 prodromal individuals’ perspective on active recruitment for early detection of α-synucleinopathies 前驱个体积极招募对早期发现α-突触核蛋白病的看法

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-09 DOI: 10.1038/s41531-025-00979-0

Sinah Röttgen, Eva Schaeffer, Annette Rogge, Ramona Hartung, Konstantin Kufer, Gereon R. Fink, Daniela Berg, Anja Ophey, Michael Sommerauer

{"title":"The prodromal individuals’ perspective on active recruitment for early detection of α-synucleinopathies","authors":"Sinah Röttgen, Eva Schaeffer, Annette Rogge, Ramona Hartung, Konstantin Kufer, Gereon R. Fink, Daniela Berg, Anja Ophey, Michael Sommerauer","doi":"10.1038/s41531-025-00979-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00979-0","url":null,"abstract":"Only the timely detection of individuals with incipient α-synucleinopathies can pave the way for developing disease-modifying therapies. Our aim was to explore the views of individuals with isolated REM sleep behavior disorder (iRBD), actively recruited from the general population, on the ethical justifiability of active recruitment and their experiences with risk disclosure. This mixed-methods study surveyed individuals with iRBD, confirmed by video-polysomnography, utilizing an interdisciplinary-developed online questionnaire. Of 99 invited individuals, 75 (75.8%) answered the survey. While 55.6% experienced the information on the increased risk as burdensome, 63.9% supported risk disclosure if consent had been obtained beforehand. Almost all individuals (96.2%) regarded our active recruitment method as appropriate, and 86.7% indicated they would participate again. Open-text responses indicated that key motivations included access to information and care, and contributing to research progress. This well-received recruitment strategy could serve as a model for future screening initiatives in α-synucleinopathy research.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930977","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

Protein-truncating variants in UQCRC1 are associated with Parkinson’s disease: evidence from half-million people UQCRC1蛋白截断变异与帕金森病相关：来自50万人的证据

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-09 DOI: 10.1038/s41531-025-00987-0

Xiaoxi Jing, Zongzhi Liu, Wenwen Li, Kaiyan Ma, Jiaxiang Zhang, Zeqi Yan, Shuo Zhang, Jiecong Lin, Junpeng Zhao, Ken K. Ong, John R. B. Perry, Yajie Zhao

引用次数: 0

Characterizing the heterogeneity of neurodegenerative diseases through EEG normative modeling 通过EEG规范建模表征神经退行性疾病的异质性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-08 DOI: 10.1038/s41531-025-00957-6

Judie Tabbal, Aida Ebadi, Ahmad Mheich, Aya Kabbara, Bahar Güntekin, Görsev Yener, Veronique Paban, Ute Gschwandtner, Peter Fuhr, Marc Verin, Claudio Babiloni, Sahar Allouch, Mahmoud Hassan

{"title":"Characterizing the heterogeneity of neurodegenerative diseases through EEG normative modeling","authors":"Judie Tabbal, Aida Ebadi, Ahmad Mheich, Aya Kabbara, Bahar Güntekin, Görsev Yener, Veronique Paban, Ute Gschwandtner, Peter Fuhr, Marc Verin, Claudio Babiloni, Sahar Allouch, Mahmoud Hassan","doi":"10.1038/s41531-025-00957-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00957-6","url":null,"abstract":"Neurodegenerative diseases like Parkinson’s (PD) and Alzheimer’s (AD) exhibit considerable heterogeneity of functional brain features within patients, complicating diagnosis and treatment. Here, we use electroencephalography (EEG) and normative modeling to investigate neurophysiological mechanisms underpinning this heterogeneity. Resting-state EEG data from 14 clinical units included healthy adults (n = 499) and patients with PD (n = 237) and AD (n = 197), aged over 40. Spectral and source connectivity analyses provided features for normative modeling, revealing significant, frequency-dependent EEG deviations with high heterogeneity in PD and AD. Around 30% of patients exhibited spectral deviations, while ~80% showed functional source connectivity deviations. Notably, the spatial overlap of deviant features did not exceed 60% for spectral and 25% for connectivity analysis. Furthermore, patient-specific deviations correlated with clinical measures, with greater deviations linked to worse UPDRS for PD (⍴ = 0.24, p = 0.025) and MMSE for AD (⍴ = −0.26, p = 0.01). These results suggest that EEG deviations could enrich individualized clinical assessment in Precision Neurology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"17 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920421","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

Prominent role of PM10 in the link between air pollution and incident Parkinson’s Disease PM10在空气污染与帕金森病发病之间的关系中的突出作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-07 DOI: 10.1038/s41531-025-00935-y

Alessandro Gialluisi, Simona Costanzo, Maria Ilenia De Bartolo, Giovanni Veronesi, Matteo Renzi, Assuntina Cembalo, Alfonsina Tirozzi, Stefania Falciglia, Moreno Ricci, Americo Bonanni, Francesco Martone, Gaetano Zazzaro, Antonietta Pepe, Daniele Belvisi, Marco Mario Ferrario, Francesco Gianfagna, Chiara Cerletti, Maria Benedetta Donati, Stefania Massari, Alfredo Berardelli, Giovanni de Gaetano, Licia Iacoviello

{"title":"Prominent role of PM10 in the link between air pollution and incident Parkinson’s Disease","authors":"Alessandro Gialluisi, Simona Costanzo, Maria Ilenia De Bartolo, Giovanni Veronesi, Matteo Renzi, Assuntina Cembalo, Alfonsina Tirozzi, Stefania Falciglia, Moreno Ricci, Americo Bonanni, Francesco Martone, Gaetano Zazzaro, Antonietta Pepe, Daniele Belvisi, Marco Mario Ferrario, Francesco Gianfagna, Chiara Cerletti, Maria Benedetta Donati, Stefania Massari, Alfredo Berardelli, Giovanni de Gaetano, Licia Iacoviello","doi":"10.1038/s41531-025-00935-y","DOIUrl":"https://doi.org/10.1038/s41531-025-00935-y","url":null,"abstract":"Air pollution has been associated with Parkinson’s Disease (PD) risk, although this relationship remains unclear. We estimated yearly levels of exposure to ten air pollutants (period 2006–2018) in an Italian population cohort, the Moli-sani study (N = 24,325; ≥35 years; 51.9% women), and derived three principal components, testing their associations with incident PD risk over 23,841 participants (213 cases, median(IQR) follow-up 11.2(2.0) years). This revealed a statistically significant association of PC1 (explaining 38.2% of common variance, tagging PM10 levels), independent on sociodemographic, professional and lifestyles covariates (Hazard Ratio [95%CI] = 1.04[1.02–1.07]). The association was confirmed testing average PM10 levels during follow-up (18[13–24]% increase of PD risk per 1 μg/m3 increase of PM10). Among different circulating markers, lipoprotein a explained a significant proportion of this association (2.8[0.9; 8.4]%). These findings suggest PM10 as a target to lower PD risk at the population level and a potential implication of lipoprotein a in PD etiology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"81 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915320","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

High-resolution mapping of substantia nigra in Parkinson’s disease using 7 tesla magnetic resonance imaging 利用7特斯拉磁共振成像对帕金森病黑质进行高分辨率成像

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-06 DOI: 10.1038/s41531-025-00972-7

Christopher F. Madelung, Annemette Løkkegaard, Søren A. Fuglsang, Marta M. Marques, Vincent O. Boer, Kristoffer H. Madsen, Anne-Mette Hejl, David Meder, Hartwig R. Siebner

{"title":"High-resolution mapping of substantia nigra in Parkinson’s disease using 7 tesla magnetic resonance imaging","authors":"Christopher F. Madelung, Annemette Løkkegaard, Søren A. Fuglsang, Marta M. Marques, Vincent O. Boer, Kristoffer H. Madsen, Anne-Mette Hejl, David Meder, Hartwig R. Siebner","doi":"10.1038/s41531-025-00972-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00972-7","url":null,"abstract":"Parkinson’s disease causes a progressive loss of dopaminergic neurons and iron accumulation in the substantia nigra pars compacta. Using ultra-high field magnetic resonance imaging (MRI) at 7 tesla in 43 Parkinson’s patients and 24 healthy controls, we analyzed the voxel-wise pattern of structural disintegration of dopamine neurons with neuromelanin-sensitive MRI, along with assessing iron accumulation using R2* and quantitative susceptibility mapping (QSM). We also explored correlations between these measures and the severity of residual motor symptoms in the on-medication state and other clinical variables. Differences were most notable in the nigrosomes within the pars compacta, with patients showing reduced neuromelanin signals and increased QSM values. Severity and asymmetry of motor symptoms correlated with higher R2* and QSM values in nigrosome N1. Thus, ultra-high field MRI provides high-resolution maps of various aspects of the underlying neurodegenerative process which reflect individual motor impairment in Parkinson’s disease.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"98 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909981","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

Modulatory effect of levodopa on the basal ganglia-cerebellum connectivity in Parkinson’s disease 左旋多巴对帕金森病基底神经节-小脑连通性的调节作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-06 DOI: 10.1038/s41531-025-00954-9

Juyoung Jenna Yun, Subati Abulikemu, Kodchakorn Love Jangwanich, Yen F. Tai, Shlomi Haar

{"title":"Modulatory effect of levodopa on the basal ganglia-cerebellum connectivity in Parkinson’s disease","authors":"Juyoung Jenna Yun, Subati Abulikemu, Kodchakorn Love Jangwanich, Yen F. Tai, Shlomi Haar","doi":"10.1038/s41531-025-00954-9","DOIUrl":"https://doi.org/10.1038/s41531-025-00954-9","url":null,"abstract":"Long-term levodopa use in Parkinson’s disease is associated with declining efficacy and motor complications. Understanding its effects on brain reorganisation is vital for optimizing therapy. Using data from Parkinson’s Progression Marker Initiative, we investigated levodopa’s impact on resting-state functional connectivity within the cortico-basal ganglia-cerebellum system in 29 patients, under drug-naïve and levodopa-medicated conditions. Univariate comparisons of inter-regional connectivity between conditions were conducted, and multivariate combinations of connections within and between networks were assessed. No significant effect of levodopa was found using the univariate seed-based approach. However, the network connectivity pattern between basal ganglia and cerebellum showed robust classification power. Eigenvector Centrality Mapping (ECM) further identified functional hubs, with cerebellar hubs being the only ones within the cortico-basal ganglia-cerebellum system affected by medication. Our study provides further insight into the importance of inter-network functional connectivity in Parkinson’s and the impact of levodopa medication, highlighting the often-overlooked role of the cerebellum.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"39 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915321","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

Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease. 帕金森病中外周和中枢犬尿氨酸通路失调的性别差异

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-06 DOI: 10.1038/s41531-025-00949-6

Leslie C Jellen,Martha L Escobar Galvis,Qiong Sha,Christine Isaguirre,Amy Johnson,Zach Madaj,Mechelle M Lewis,Ryan D Sheldon,Lan Kong,Xuemei Huang,Lena Brundin

{"title":"Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson's disease.","authors":"Leslie C Jellen,Martha L Escobar Galvis,Qiong Sha,Christine Isaguirre,Amy Johnson,Zach Madaj,Mechelle M Lewis,Ryan D Sheldon,Lan Kong,Xuemei Huang,Lena Brundin","doi":"10.1038/s41531-025-00949-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00949-6","url":null,"abstract":"We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson's disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD (\"OFF\"), 86 controls); CSF: n = 183 (108, 75). Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in females. These 10 markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP dysregulation in PD that is associated with worse symptoms and more prevalent in women. This work shows that KP dysregulation in peripheral and central compartments is linked to symptom severity in PD and warrants further systematic studies unraveling sex-dependent metabolic differences.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"16 1","pages":"116"},"PeriodicalIF":8.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914990","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