Journal of Parkinson's disease最新文献

{"title":"SynNeurGe: The road ahead for a biological definition of Parkinson's disease.","authors":"Günter U Höglinger, Anthony E Lang","doi":"10.1177/1877718X241298194","DOIUrl":"10.1177/1877718X241298194","url":null,"abstract":"<p><p>While significant progress has been made in treating Parkinson's disease (PD) symptoms, disease-modifying therapies (DMTs) have consistently failed. To address the underlying molecular mechanisms of PD, two biology-based criteria have been proposed: the \"Synucleinopathy-Neurodegeneration-Genetics\" (SynNeurGe) and \"neuronal α-synuclein disease\" (NSD) frameworks. Both frameworks emphasize the importance of biological markers over clinical symptoms. They recognize α-synuclein aggregation and genetic mutations (such as SNCA) as key diagnostic elements, with α-synuclein seed amplification assays (SAA) in cerebrospinal fluid (CSF) used to detect early disease stages. Dopaminergic neurodegeneration, measured by DAT imaging, is also central to both frameworks. These shared features aim to improve early diagnosis and precision medicine for PD. However, SynNeurGe provides a broader, more flexible framework that integrates α-synuclein pathology (S), neurodegeneration (N), and genetics (G), linked to clinical features (C). It aims to accommodate the complexity of PD and related Lewy body diseases, facilitating research on targeted DMTs. In contrast, NSD focuses specifically on PD and Lewy body dementia, introducing a staging system (NSD-ISS) based on biological markers and clinical impairment, helping track disease progression from preclinical to symptomatic stages. Despite their differences, both approaches highlight the need for more specific biomarkers and prospective studies to improve early intervention and personalized treatment. Harmonizing SynNeurGe and NSD concepts will be key in creating a universally accepted framework for precise PD diagnosis and therapy development.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"931-938"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposed biological definitions of Parkinson's disease confuse understanding without delivering meaningful advances.","authors":"Francisco Cardoso, Peter Schmidt","doi":"10.1177/1877718X241308482","DOIUrl":"10.1177/1877718X241308482","url":null,"abstract":"<p><p>This article reflects on two proposals to classify and stage Parkinson's disease (PD) and related conditions based on the presence of aggregated alpha-synuclein (ASN) detected by alpha-synuclein aggregation assay (SAA). The authors highlight the significant shortcomings of the proposals: detection of ASN by SAA is not specific of PD or other well-established clinical conditions; they do not allow prediction of clinical course and prognosis; and they are not suitable as an endpoint for clinical trials. To move forward with proposals reflecting so many uncertainties and unknowns will just sow confusion and misunderstanding within the PD community.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"939-943"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the neural network of freezing of gait in Parkinson's disease: A coordinate-based network study.","authors":"Chiara Camastra, Antonio Augimeri, Aldo Quattrone, Andrea Quattrone","doi":"10.1177/1877718X251348669","DOIUrl":"10.1177/1877718X251348669","url":null,"abstract":"<p><p>BackgroundFreezing of gait (FoG) is a debilitating symptom in Parkinson's disease (PD), yet its pathophysiological mechanisms remain poorly understood. Several studies have investigated the FoG neuroimaging correlates, with heterogeneous results.ObjectiveThis study investigated in a large PD cohort whether the disparate neuroimaging findings may converge to a common brain network.MethodsT1-weighted MRI scans of 500 PD patients (90 with FoG [PD-FoG] and 410 without FoG [PD-nFoG]) were acquired from the Parkinson's Progression Markers Initiative. A voxel-based morphometry (VBM) analysis was conducted to identify clusters of decreased grey matter (GM) in PD-FoG patients. Subsequently, VBM coordinates of significant clusters were used as seed regions to generate connectivity network maps using a large functional normative connectome, and these maps were overlapped to identify regions connected with most VBM clusters.ResultsPD-FoG patients showed GM atrophy in cerebellar lobes, hippocampus, putamen, insula, inferior temporal gyrus and lateral orbitofrontal gyrus compared with PD-nFoG patients. Network analysis revealed that these regions colocalized within a specific brain network focused on midbrain, substantia nigra, subthalamic nucleus, globus pallidus, inferior putamen and dorsal medial cerebellum. These findings were confirmed by using coordinates from previous VBM studies for the network analysis, validating our results.ConclusionsThis study revealed a brain network underlying FoG in PD, reducing the heterogeneity of previous neuroimaging evidence on FoG. These results may represent a significant step forward in the understanding of FoG and may be relevant for optimized targeted neuro-modulatory treatments to reduce FoG in PD patients.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"982-989"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the link between personality dimensions and non-motor fluctuations in Parkinson's disease.","authors":"Mathilde Boussac, Florent Faggianelli, Estelle Harroch, Alexandre Eusebio, Margherita Fabbri, Fabienne Ory-Magne, Emeline Descamps, Olivier Rascol, Chloé Laurencin, Ana-Raquel Marques, Mathieu Anheim, Bruno Giordana, Lucie Hopes, Caroline Moreau, Anne-Sophie Rolland, David Devos, David Maltête, Solène Ansquer, Elodie Hainque, Sophie Drapier, Jean-Philippe Brandel, Tiphaine Rouaud, Dominique Guehl, Bechir Jarraya, Mélissa Tir, Tatiana Witjas, Jean-Philippe Azulay, Christine Brefel-Courbon","doi":"10.1177/1877718X251354932","DOIUrl":"10.1177/1877718X251354932","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.ObjectiveWe evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).MethodsFrom the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0). NMFs were evaluated using the NMFs Severity Scale at V0 and one year after STN-DBS (V1). Linear regression models were performed between TCI dimensions and NMFs at V0; and logistic regression models were done between TCI dimensions and 1) groups of dopa-sensitive patients (responders to ON medication at V0) versus non-dopa-sensitive ones, and 2) responders versus non-responders to STN-DBS at V1. Odds ratios (OR) were also calculated.ResultsSignificant associations were found between two TCI personality dimensions (\"Harm Avoidance\" and \"Self-Directedness\") and severity of NMFs in OFF medication at V0: PD patients with higher Harm Avoidance and lower Self-Directedness scores having more NMFs. TCI personality dimensions were not associated with the dopa-sensitivity while Novelty Seeking was significantly associated with the STN-DBS-responder group for the psychiatric (OR = 1.09 [1.02-1.17]) and for the dysautonomic NMFs (OR = 1.11 [1.04-1.18]).ConclusionsCertain personality dimensions (Harm Avoidance and Self-Directedness) are associated with NMFs severity at baseline, and PD patients with high Novelty Seeking seem to be better candidates for NMFs improvement after STN-DBS.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1007-1018"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease associated with <i>LRRK2</i>-R1441C mutation: Characterization and comparison with other <i>LRRK2</i> mutations.","authors":"Rafi Hadad, Roy N Alcalay, Inna Senderova, Maria Nassar, Andjelika Milicic, Judith Aharon Peretz, Isabel Elaine Allen, Rachel Ben-Hayun, Natalia Chasnyk, Ilham Morani, Nadav Elkoshi, Victor Valcour, Ilana Schlesinger","doi":"10.1177/1877718X251354986","DOIUrl":"10.1177/1877718X251354986","url":null,"abstract":"<p><p>Mutations in the leucine-rich repeat kinase 2 (<i>LRRK2</i>) gene associate with familial and sporadic Parkinson's disease (PD). While various <i>LRRK2</i> allelic variants have been studied, characteristics of R1441C carriers remain underexplored. We compared PD patients carrying the R1441C mutation (90% Israeli Arabs) to those carrying the G2019S (70% Ashkenazi Jews) and R1441G (42% Basque) variants. R1441C carriers exhibited a distinct clinical phenotype characterized by severe motor and non-motor symptoms and worse scores on the Montreal Cognitive Assessment. These findings highlight the importance of ethnic diversity and genetic stratification in PD research. These results need confirmation in larger, more diverse samples.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1029-1034"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding barriers and facilitators to participation in Parkinson's research in Black communities in the UK.","authors":"Ivelina Dobreva, Sabrina Kalam, Moïse Roche, Ece Bayram, Rimona S Weil, Angeliki Zarkali","doi":"10.1177/1877718X251351990","DOIUrl":"10.1177/1877718X251351990","url":null,"abstract":"<p><p>People from Black backgrounds are underrepresented in Parkinson's research, despite evidence of higher disease burden and risk of dementia. Greater understanding of the factors influencing participation in Parkinson's research can improve recruitment, quality and generalizability of both observational research studies and clinical trials. Through focus groups with 17 people with Parkinson's and carers from Black communities, we identified distrust in the research process, stigma of Parkinson's diagnosis, and accessibility as key barriers to research participation. Participants made recommendations including: raising awareness of Parkinson's and related research, involving community ambassadors, improving communication throughout the research process, and providing practical support.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1035-1039"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A perspective of persons with Parkinson's disease on the contribution of alpha-synuclein seed amplification assay biomarker to the diagnosis of Parkinson's disease.","authors":"Susanne Bowen, David Blacker, Richard Prettyman","doi":"10.1177/1877718X251315651","DOIUrl":"10.1177/1877718X251315651","url":null,"abstract":"<p><p>Alpha-synuclein is a normal protein, but misfolded forms in the cerebrospinal fluid can be detected using the alpha-synuclein seed amplification assay (αSyn-SAA), a potential biomarker for Parkinson's disease (PD). Some experts consider this assay a 'game changer' for redefining and reclassifying PD. In this article, we, three individuals with PD, share our perspective on the suitability of αSyn-SAA as the basis for a new classification and staging system for PD. We also discuss other biomarkers and their relevance to those with PD, drawing on our research and the scientific background of two authors. We aim to clarify complex media reports and study findings for the PD community. We argue that while αSyn-SAA can identify the presence of pathology, it cannot explain the underlying cause for such pathology or predict the progression of PD. Given the varied biological pathways leading to PD, using αSyn-SAA as a unified biological definition for a new classification system is premature. Further research is needed before it can serve as the foundation for defining and staging Parkinson's disease. Although αSyn-SAA has its place, like the DAT scan, it should be seen as a tool for confirming diagnoses rather than defining them.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"953-956"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced expression of <i>Pss</i> gene in <i>Drosophila</i> cortex glia causes dopaminergic cell death.","authors":"Banya Pak, Chaeeun Kim, Seung-Hae Kwon, Joon-Kyu Lee, Sang-Hak Jeon","doi":"10.1177/1877718X251349407","DOIUrl":"10.1177/1877718X251349407","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. While abnormal protein aggregation has been classically implicated in PD, increasing evidence suggests that lipid dysregulation may also contribute to neuronal vulnerability. Recent studies have begun to link abnormal phosphatidylserine (PS) metabolism to mitochondrial impairment and dopaminergic neuron loss in PD, yet the underlying cellular mechanisms remain poorly defined.ObjectiveThis study aimed to determine how impaired PS synthesis in cortex glia affects mitochondrial function, oxidative stress, and dopaminergic neuron survival, using a <i>Drosophila</i> model of glia-specific <i>Phosphatidylserine synthase</i> (<i>Pss</i>) knockdown.MethodsTo dissect the glial contribution to PS-related neurodegeneration, we employed a <i>Drosophila</i> model in which the <i>Pss</i> gene was selectively knocked down in cortex glia using the GAL4-UAS system. We evaluated PD-like phenotypes by assessing the number of dopaminergic neurons in the PPL1 and PPL2 clusters, as well as locomotor activity and lifespan, following glia-specific knockdown of <i>Pss</i> gene.ResultsCortex glia-specific knockdown of <i>Pss</i> impaired locomotion and reduced lifespan in flies, indicating a systemic decline in neuronal and mitochondrial function. <i>Pss</i> knockdown reduced <i>mitochondrial transcription factor A</i> (<i>Tfam</i>) expression, disrupted mitochondrial gene expression, and elevated ROS levels. Western blot analysis also revealed reduced AKT phosphorylation without changes in total AKT. These results ultimately lead to loss of dopaminergic neurons.ConclusionsThese findings establish a mechanistic link among abnormal PS metabolism, impaired AKT signaling, mitochondrial dysfunction, and dopaminergic neuron loss. Our study provides novel evidence that glia-driven abnormalities in PS metabolism may cause PD-like neurodegeneration, offering mechanistic insights and potential therapeutic targets.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"957-969"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tackling gender in progressive supranuclear palsy: Male patients present more apathy.","authors":"Lan Ye, Stephan Greten, Ida Wilkens, Florian Wegner, Lea Krey, Matthias Höllerhage, Monika Pötter-Nerger, Molly Zeitzschel, Keno Hagena, Jan Kassubek, Patrick Süß, Jürgen Winkler, Daniela Berg, Steffen Paschen, Lars Tönges, Doreen Gruber, Florin Gandor, Wolfgang H Jost, Andrea A Kühn, Inga Claus, Tobias Warnecke, David J Pedrosa, Carsten Eggers, Claudia Trenkwalder, Joseph Classen, Johannes Schwarz, Alfons Schnitzler, Günter U Höglinger, Martin Klietz","doi":"10.1177/1877718X251343094","DOIUrl":"10.1177/1877718X251343094","url":null,"abstract":"<p><p>Gender differences in progressive supranuclear palsy (PSP) may become relevant for clinical trials, treatment decisions and patient counseling. To study gender associated differences we conducted a retrospective data analysis of 191 male and 157 female PSP patients from a large multicenter observational cohort in Germany. While no differences in motor skills, disease severity, daily living abilities, global cognitive status and depressive symptoms were observed between genders, male patients showed significantly higher apathy scores, a finding also noted in other neurological diseases. In this study, apart from male patients exhibiting higher levels of apathy, no significant disease-specific gender differences were observed in PSP patients.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1024-1028"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge and utilization of compensation strategies for Parkinson's disease in Dutch long-term care facilities: A survey among 130 healthcare professionals.","authors":"Ties J Gaveel, Anouk Tosserams, Maarten J Nijkrake, Jorik Nonnekes","doi":"10.1177/1877718X251354928","DOIUrl":"10.1177/1877718X251354928","url":null,"abstract":"<p><p>BackgroundCompensation strategies have been shown to improve functional mobility in people with Parkinson's disease (PD) who live independently. However, knowledge on its utilization in in long-term care (LTC) settings is unknown.ObjectiveThis study aimed to establish the knowledge and utilization of compensation strategies for functional mobility for individuals with PD among healthcare professionals working in LTC facilities in the Netherlands. Secondary aims included assessing subgroup differences among healthcare professionals and exploring perceived barriers to utilizing these strategies in LTC.MethodsA cross-sectional online survey design was conducted with (allied) healthcare professionals working in LTC facilities across the Netherlands.ResultsOverall knowledge and utilization of compensation strategies among 130 healthcare professionals was high, with a median of 5 out of 7 known categories, 4 out of 7 used for gait, and 3 out of 5 for transfers. Variations among professions existed, with physiotherapists and occupational therapists demonstrating higher scores than nurses and personal care assistants. Professionals specifically trained in PD care and those working in specialized PD departments demonstrated a higher level of knowledge. Main identified barriers for utilization were limited knowledge and time of the healthcare professionals, and concerns regarding limited feasibility in patients with severe cognitive impairments.ConclusionsWhile knowledge and utilization of compensation strategies for PD in LTC facilities was widespread, the findings highlight a need for tailored training programs for healthcare professionals to improve patient care. Future research should evaluate the feasibility and usefulness of such training programs.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"990-997"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}