Journal of Parkinson's disease最新文献

{"title":"<i>P2RX7,</i> an adaptive immune response gene, is associated with Parkinson's disease risk and age at onset.","authors":"Shachar Shani, Mali Gana-Weisz, Anat Bar-Shira, Avner Thaler, Tanya Gurevich, Anat Mirelman, Nir Giladi, Roy N Alcalay, Avi Orr-Urtreger, Orly Goldstein","doi":"10.1177/1877718X241296015","DOIUrl":"https://doi.org/10.1177/1877718X241296015","url":null,"abstract":"<p><strong>Background: </strong>The adaptive immune response has a role in Parkinson's disease (PD). Patients with <i>LRRK2</i> or <i>GBA1</i> mutations often exhibit distinct clinical characteristics.</p><p><strong>Objective: </strong>To evaluate the involvement of adaptive immune response genes in three PD groups: <i>GBA1</i>-PD, <i>LRRK2</i>-PD, and non-carrier (NC)-PD.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) associated with PD were identified using four datasets. Of them, adaptive immune response genes were evaluated using whole-genome-sequencing of 201 unrelated Ashkenazi-Jewish (AJ) PD patients. Potential pathogenic variants were identified, and <i>P2RX7</i> variants were assessed in 1200 AJ-PD patients. Burden analysis of rare variants (allele frequencies (AF) < 0.01) on disease risk, and association analyses of common variants (AF ≥ 0.01) with disease risk and age-at-onset (AAO) were conducted. AFs were compared to AJ-non-neuro cases reported in gnomAD. Variants associated with PD were further examined in an independent AJ cohort from AMP-PD.</p><p><strong>Results: </strong>Of the four adaptive immune DEGs identified, <i>CD8B2, P2RX7</i>, <i>IL27RA</i>, and <i>ZC3H12A</i>, three common variants in <i>P2RX7</i> were statistically significant: Tyr155His was associated with NC-PD (allelic OR = 1.15, <i>p </i>= 0.015) ; Arg276His was associated with <i>LRRK2</i>-PD (allelic OR = 2.10, <i>p </i>= 0.037), while Glu496Ala was associated with earlier AAO in <i>LRRK2</i>-PD (<i>p </i>= 0.014). Burden analysis showed no significant effect on PD-risk. In the AMP-PD cohort, odds ratios of the two risk variants were similar to the primary cohort, but did not reach significance, probably due to small control sample size (n = 263).</p><p><strong>Conclusions: </strong>Common variants within <i>P2RX7</i> are likely associated with PD-risk and earlier AAO. These findings further suggest <i>P2RX7</i>'s involvement in PD and its potential interplay with <i>LRRK2</i>.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 8","pages":"1575-1583"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433484","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":"Motor outcomes in unilateral, bilateral rapid, and bilateral delayed staging deep brain stimulation for Parkinson's disease.","authors":"Filipe Sarmento, Anshul Daga, Anson Wang, Venkat Srikar Lavu, Tiberio de Araújo, Sina Aghili Mehrizi, Justin D Hilliard, Reza Forghani, Michael S Okun, Joshua K Wong","doi":"10.1177/1877718X241296014","DOIUrl":"https://doi.org/10.1177/1877718X241296014","url":null,"abstract":"<p><strong>Background: </strong>Deep brain stimulation (DBS) is effective in managing motor symptoms in select cases of Parkinson's disease (PD). Nonetheless, the ideal timing for surgery and the comparative outcomes of unilateral versus bilateral DBS procedures remain under-researched areas.</p><p><strong>Objective: </strong>We aimed to compare the impact of unilateral and bilateral DBS on the motor manifestations of PD using standardized Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III).</p><p><strong>Methods: </strong>We conducted a retrospective analysis of PD patients who underwent multidisciplinary DBS screening which made a formal recommendation for surgical approach. We compared unilateral, bilateral \"rapid\" (less than 2 months apart), and bilateral \"staged\" (5-11 months apart) implantation approaches. The study included 90 patients, 48 patients, and 42 patients from the 3 groups, respectively. The primary outcome was the percentage improvement in baseline off UPDRS-III scores compared to medication-off/DBS-on conditions at 3-6 months and 10-14 months post-surgery. Mann-Whitney U tests were used to compare scores within groups and across follow-up periods. The Kruskal-Wallis test assessed differences among groups. Furthermore, multiple regression analyses were performed to adjust for confounding variables.</p><p><strong>Results: </strong>UPDRS-III scores improved significantly from baseline at both follow-up intervals regardless of the type of DBS staging approach. The Kruskal-Wallis test revealed no significant differences in UPDRS-III percentage improvement among groups at 3-6 months (p = 0.125) and 10-14 months (p = 0.298) post-DBS.</p><p><strong>Conclusions: </strong>Our study revealed that in a single experienced DBS center which employed multidisciplinary screening, assignment to unilateral and bilateral DBS, both rapid and staged, targeting the STN or GPi, effectively improved motor symptoms for up to 14 months.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 8","pages":"1614-1622"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433509","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":"Structurally targeted mutagenesis identifies key residues supporting α-synuclein misfolding in multiple system atrophy.","authors":"Patricia M Reis, Sara Am Holec, Chimere Ezeiruaku, Matthew P Frost, Christine K Brown, Samantha L Liu, Steven H Olson, Amanda L Woerman","doi":"10.3233/JPD-240296","DOIUrl":"10.3233/JPD-240296","url":null,"abstract":"<p><strong>Background: </strong>Multiple system atrophy (MSA) and Parkinson's disease (PD) are caused by misfolded α-synuclein spreading throughout the central nervous system. While familial PD is linked to several α-synuclein mutations, no mutations are associated with MSA. We previously showed that the familial PD mutation E46K inhibits replication of MSA prions both <i>in vitro</i> and <i>in vivo</i>, providing key evidence to support the hypothesis that α-synuclein adopts unique strains in patients.</p><p><strong>Objective: </strong>Here we sought to further interrogate α-synuclein misfolding to identify the structural determinants that contribute to MSA strain biology.</p><p><strong>Methods: </strong>We engineered a panel of cell lines harbouring both PD-linked and novel mutations designed to identify key residues that facilitate α-synuclein misfolding in MSA. We also used Maestro <i>in silico</i> analyses to predict the effect of each mutation on α-synuclein misfolding into one of the reported MSA cryo-electron microscopy conformations.</p><p><strong>Results: </strong>In many cases, our modelling accurately identified mutations that facilitated or inhibited MSA replication. However, Maestro was occasionally unable to predict the effect of a mutation, demonstrating the challenge of using computational tools to investigate intrinsically disordered proteins. Finally, we used our cellular models to determine the mechanism underlying the E46K-driven inhibition of MSA replication, finding that the E46/K80 salt bridge is necessary to support α-synuclein misfolding.</p><p><strong>Conclusions: </strong>Our studies used a structure-based approach to investigate α-synuclein misfolding, resulting in the creation of a powerful panel of cell lines that can be used to interrogate MSA strain biology.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 8","pages":"1543-1558"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433049","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":"Winding Back the Clock on Advanced Therapies: It's Time to Get Smart.","authors":"Matthew J Georgiades,Anton A van der Plas,Bastiaan R Bloem,Simon J G Lewis","doi":"10.3233/jpd-240193","DOIUrl":"https://doi.org/10.3233/jpd-240193","url":null,"abstract":"Our language affects patients' perceptions of therapies. In Parkinson's disease, emergent response fluctuations and dyskinesias typically trigger conversations around commencing an \"Advanced Therapy\" which carries notions of Advanced Disease. The patient, resolute in their commitment to fighting the disease, is misled. Chasing reassurance that their disease has not yet progressed considerably; they may therefore resist a potentially life-changing therapy. Instead, we should offer a \"Smart Therapy\". This term more accurately and positively describes therapies on offer that stabilize response fluctuations and improve quality of life, without a focus on the negative connotations of progression to more advanced disease.","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"4 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260003","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":"Prospective Study of Lung Function with Prodromal, Clinical Parkinson's Disease, and Mortality.","authors":"Xiao Chen,Zhicheng Zhang,Lin Tong,Han Wang,Xinming Xu,Liang Sun,Yaqi Li,Xiang Gao","doi":"10.3233/jpd-240097","DOIUrl":"https://doi.org/10.3233/jpd-240097","url":null,"abstract":"BackgroundThe association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown.ObjectiveTo prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank.MethodsIncluded were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations.ResultsPoor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02- 1.37) for FEV1, 1.14 (95% CI, 0.99- 1.29) for FVC, and 1.23 (95% CI, 1.08- 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD.ConclusionsThe current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality.","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"55 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260001","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":"Non-Pharmacological Interventions for People with Parkinson's Disease: Are We Entering a New Era?","authors":"E Kalbe, B R Bloem, L V Kalia, A Nieuwboer","doi":"10.3233/JPD-249006","DOIUrl":"https://doi.org/10.3233/JPD-249006","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468784","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":"Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson’s Disease","authors":"Elena Giusto, Lorenza Maistrello, Lucia Iannotta, Veronica Giusti, Ludovica Iovino, Rina Bandopadhyay, Angelo Antonini, Luigi Bubacco, Rita Barresi, Nicoletta Plotegher, Elisa Greggio, Laura Civiero","doi":"10.3233/jpd-230402","DOIUrl":"https://doi.org/10.3233/jpd-230402","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>Background:</h3><p>\u0000Parkinson’s disease is a progressive neurodegenerative disorder mainly distinguished by sporadic etiology, although a genetic component is also well established. Variants in the <i>LRRK2</i> gene are associated with both familiar and sporadic disease. We have previously shown that PAK6 and 14-3-3γ protein interact with and regulate the activity of LRRK2.</p><h3><span></span>Objective:</h3><p>\u0000The aim of this study is to quantify PAK6 and 14-3-3γ in plasma as reliable biomarkers for the diagnosis of both sporadic and LRRK2-linked Parkinson’s disease.</p><h3><span></span>Methods:</h3><p>\u0000After an initial quantification of PAK6 and 14-3-3γ expression by means of Western blot in post-mortem human brains, we verified the presence of the two proteins in plasma by using quantitative ELISA tests. We analyzed samples obtained from 39 healthy subjects, 40 patients with sporadic Parkinson’s disease, 50 LRRK2-G2019S non-manifesting carriers and 31 patients with LRRK2-G2019S Parkinson’s disease.</p><h3><span></span>Results:</h3><p>\u0000The amount of PAK6 and 14-3-3γ is significantly different in patients with Parkinson’s disease compared to healthy subjects. Moreover, the amount of PAK6 also varies with the presence of the G2019S mutation in the LRRK2 gene. Although the generalized linear models show a low association between the presence of Parkinson’s disease and PAK6, the kinase could be added in a broader panel of biomarkers for the diagnosis of Parkinson’s disease.</p><h3><span></span>Conclusions:</h3><p>\u0000Changes of PAK6 and 14-3-3γ amount in plasma represent a shared readout for patients affected by sporadic and LRRK2-linked Parkinson’s disease. Overall, they can contribute to the establishment of an extended panel of biomarkers for the diagnosis of Parkinson’s disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"29 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806095","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":"Neural Oscillations and Functional Significances for Prioritizing Dual-Task Walking in Parkinson’s Disease","authors":"Cheng-Ya Huang, Yu-An Chen, Ruey-Meei Wu, Ing-Shiou Hwang","doi":"10.3233/jpd-230245","DOIUrl":"https://doi.org/10.3233/jpd-230245","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>Background:</h3><p>Task prioritization involves allocating brain resources in a dual-task scenario, but the mechanistic details of how prioritization strategies affect dual-task walking performance for Parkinson’s disease (PD) are little understood.</p><h3><span></span>Objective:</h3><p>We investigated the performance benefits and corresponding neural signatures for people with PD during dual-task walking, using gait-prioritization (GP) and manual-prioritization (MP) strategies.</p><h3><span></span>Methods:</h3><p>Participants (N = 34) were asked to hold two inter-locking rings while walking and to prioritize either taking big steps (GP strategy) or separating the two rings (MP strategy). Gait parameters and ring-touch time were measured, and scalp electroencephalograph was performed.</p><h3><span></span>Results:</h3><p>Compared with the MP strategy, the GP strategy yielded faster walking speed and longer step length, whereas ring-touch time did not significantly differ between the two strategies. The MP strategy led to higher alpha (8–12 Hz) power in the posterior cortex and beta (13–35 Hz) power in the left frontal-temporal area, but the GP strategy was associated with stronger network connectivity in the beta band. Changes in walking speed and step length because of prioritization negatively correlated with changes in alpha power. Prioritization-related changes in ring-touch time correlated negatively with changes in beta power but positively with changes in beta network connectivity.</p><h3><span></span>Conclusions:</h3><p>A GP strategy in dual-task walking for PD can enhance walking speed and step length without compromising performance in a secondary manual task. This strategy augments attentional focus and facilitates compensatory reinforcement of inter-regional information exchange.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"43 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140045638","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":"U.S. Tax Credits to Promote Practical Proactive Preventative Care for Parkinson’s Disease","authors":"Michael S. Okun","doi":"10.3233/jpd-240046","DOIUrl":"https://doi.org/10.3233/jpd-240046","url":null,"abstract":"<h4><span>Abstract</span></h4><p>Persons with Parkinson’s disease (PD) and society at large can profit from a strategic investment into a forward leaning, practical, preventative, and proactive multidisciplinary care policy. The American healthcare system is not easily bent to accommodate this type of care, and thus a tax benefit is an attractive option. An individual federal income tax benefit of $6200 each year for every person residing in the US with a diagnosis of PD, could among other offerings provide monthly access to a licensed clinical social worker and access to mental health services. The implementation of more coordinated care has the potential reduce the burden of depression, anxiety, and demoralization. Personal training would also be covered and directed by physical and occupational therapists. The combination of home-based and telemedicine services would have the added benefit of improving access. The tax benefit would also provide access to a dietician. This type of care strategy could be designed to proactively identify early signs of aspiration and urinary tract infections to ‘head off’ significant morbidity. A $6200/year individual tax benefit for those diagnosed with PD will thus translate into more fall prevention, more care in the home setting, less hospitalizations, less depression, less anxiety, less demoralization, better diets, and less persons placed in nursing facilities. Additionally, this tax benefit will provide the potential for billions of dollars in savings to the healthcare system. A tax benefit for PD is a practical preventative and proactive strategy which can serve to advantage both this generation and the next.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"301 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140045525","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":"Dietary Interventions in Parkinson’s Disease","authors":"Indy van der Berg, Sabine Schootemeijer, Karin Overbeek, Bastiaan R. Bloem, Nienke M. de Vries","doi":"10.3233/jpd-230366","DOIUrl":"https://doi.org/10.3233/jpd-230366","url":null,"abstract":"<h4><span>Abstract</span></h4><p>Several dietary patterns and nutritional supplements have been linked to the development, progression, and symptomatic treatment of Parkinson’s disease (PD). Most of the evidence, at this point, is preliminary and based largely on observational studies. Interventional studies are scarce, so the evidence on effectiveness remains inconclusive. Dietary interventions could, analogous to exercise, potentially have a beneficial effect on disease symptoms as well as on the progression of the disease and should therefore be researched in high quality studies. Further work is also needed to study whether dietary interventions, when applied to an at-risk population, have any potential to postpone the onset of manifest PD. In this paper, we summarize all ongoing clinical trials on dietary interventions in PD. We found 10 ongoing studies, all aimed at a different intervention. These studies are mostly exploratory in nature or represent phase I or phase II trials focusing on safety, biological responses, and symptomatic effects. Taken together, we conclude that research on dietary interventions in persons with PD is still in its early days. The results of the various ongoing trials are expected to generate new hypotheses and will help to shape the agenda for future research on this important topic.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"47 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139554319","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}