Degenerative neurological and neuromuscular disease最新文献

{"title":"Disabilities and Health-Related Quality of Life in Multiple Sclerosis: Prospective 10-year Web-Based Study of a Population-Based Real-Life Cohort in the Netherlands.","authors":"Peter Joseph Jongen, Ayshe Yaylali, Ingrid E H Kremer, Marco Heerings, Esther van Noort, Jitse P van Dijk, Lloyd Brandts, Ghislaine van Mastrigt","doi":"10.2147/DNND.S604437","DOIUrl":"10.2147/DNND.S604437","url":null,"abstract":"<p><strong>Purpose: </strong>To assess at population level long-term changes in disabilities and health-related quality of life (HRQoL) in persons with multiple sclerosis (PwMS) in the Netherlands.</p><p><strong>Patients and methods: </strong>A prospective web-based study in a real-world population-based self-enrolled cohort; 6-month assessments by means of the Multiple Sclerosis Impact Profile (MSIP) and Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaires; Generalized Linear Mixed Models (GLMM) analysis; predetermined anchor points 5, 8 and 10 years follow-up.</p><p><strong>Results: </strong>Nation-wide 391 patients started (2011-2012), 272 participants were included in the MSIP and 267 in the MSQoL-54 analyses. Female 74%, mean (standard deviation) age 45 (11) years. Baseline Expanded Disability Status Scale scores: 58.9% 0.0-4.0, 35.5% 4.5-6.5, 5.6% >6.5. Baseline demographic and disease characteristics did not differ between participants with and without follow-up data. GLMM indicated that after 10 years disability related to Activities of Daily Living and Basic Movement Activities had increased. Conversely, at 5, 8 and 10 years an improvement was reported in disability related to Lack of Support from Environmental Factors, more specifically Professional Care and Assistance, and Social Security Services. The other MSIP disabilities and symptoms remained stable over time, as did the physical and mental MSQoL-54 scores.</p><p><strong>Conclusion: </strong>Our findings indicate that in the Dutch MS population in the period 2011-2021 the limitations in activities of daily living and in basic movement activities worsened over time. The improved support from professional care, professional assistance and social security services may be related to the implementation of nation-wide decentralized legislation to support people with disabilities, and the emergence of MS-specific neurological and nursing care. These findings at population level regarding the long-term course of disabilities and HRQoL in PwMS in the Netherlands in the era of (high) efficacy disease-modifying drugs may be useful for policymakers, healthcare providers, and patient organizations.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"604437"},"PeriodicalIF":9.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine in Alzheimer's Disease: Evidence from Animal Models and Human Studies.","authors":"Francesco Angelucci, Jiří Cerman, Jana Amlerova, Katerina Sheardova, Jan Pavlik, Jakub Hort","doi":"10.2147/DNND.S608341","DOIUrl":"10.2147/DNND.S608341","url":null,"abstract":"<p><p>Spermidine is a naturally occurring polyamine involved in multiple cellular processes, including growth regulation, protein translation, and autophagy. Increasing attention has been devoted to its potential neuroprotective effects, particularly in Alzheimer's disease (AD), a neurodegenerative disorder characterized by β-amyloid and phosphorylated tau accumulation, synaptic dysfunction, and progressive neuronal loss. In this narrative review, we examine potential mechanisms through which spermidine may influence AD pathophysiology and summarize available preclinical and clinical evidence. Preclinical studies indicate that spermidine induces autophagy, a key cellular clearance pathway responsible for removing damaged organelles and aggregated proteins. Because impaired neuronal autophagy contributes to the accumulation of β-amyloid and tau in AD, increasing intracellular spermidine levels may enhance the degradation of these toxic species. In addition, spermidine exhibits anti-inflammatory and antioxidant properties, attenuates microglial activation, and supports mitochondrial function. In animal models of AD and brain aging, spermidine administration has been associated with improvements in cognitive performance and synaptic function. However, human clinical evidence remains limited and largely inconclusive. Observational studies suggest associations between higher dietary spermidine intake and better cognitive outcomes, but do not establish causality. Randomized clinical trials to date are few, include small and heterogeneous populations, and have not demonstrated consistent effects on primary cognitive endpoints. Overall, spermidine represents a biologically plausible modulator of pathways relevant to neurodegeneration, but translation of preclinical findings into clinical benefit remains uncertain. Current evidence is insufficient to support its use as a therapeutic or preventive intervention in AD, and further well-designed clinical studies are required to clarify its efficacy and mechanisms of action.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"608341"},"PeriodicalIF":9.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marked Clinical Improvement in Parkinson's Disease Following Double-Filtration Apheresis: A Case Report.","authors":"Harald Burgard","doi":"10.2147/DNND.S594425","DOIUrl":"10.2147/DNND.S594425","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the fastest growing progressive neurological disorder globally, characterized by motor symptoms such as bradykinesia, rigidity, resting tremor as well as a wide range of non-motor manifestations. Here, we report the case of a patient with advanced Parkinson's disease diagnosed for PD more than 12 years ago; clinical symptoms included a coarse resting tremor with a focus on the right arm and leg, gait and postural disturbances, sleep disorders and autonomic disfunctions. The patient received several medications for correction of dopamine deficiency, but clinical symptoms progressed over the years. We applied a series of double-filtration apheresis treatments and experienced marked symptomatic improvement, with near-complete resolution of motor deficits and strong decrease of MDS-UPDRS part III score. This case suggests a potential role of extracorporeal blood purification in the management of PD.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"594425"},"PeriodicalIF":9.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(Z)-Endoxifen as a Potential Modulator of Utrophin Pathways in Duchenne Muscular Dystrophy: A Mechanistic and Transcriptomic Perspective.","authors":"H Lawrence Remmel, Sandra S Hammer, Scott M Blackburn, Steven C Quay","doi":"10.2147/DNND.S574524","DOIUrl":"10.2147/DNND.S574524","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a fatal X-linked neuromuscular disorder caused by mutations in the dystrophin gene, leading to sarcolemmal instability, chronic calcium overload, mitochondrial dysfunction, inflammation, and fibrosis. These effects manifest clinically as muscle atrophy, loss of mobility, and respiratory and cardiac insufficiencies. Although gene-targeted approaches such as exon skipping and microdystrophin delivery have advanced, their applicability is restricted by genotype and adverse effects. Thus, reasonably safe, effective therapies remain a critical unmet need. (Z)-endoxifen, the (Z)-isomer of endoxifen, is the principal active metabolite of tamoxifen, exhibiting higher potency in protein kinase C (PKC) inhibition than tamoxifen and regulating various protein activities differently than tamoxifen. This pharmacologic profile positions endoxifen to address multiple DMD pathological mechanisms simultaneously. Recent literature supports the prior hypothesis that endoxifen exerts pleiotropic benefits in DMD. Transcriptomic and preclinical evidence shows that endoxifen may have superior effects to tamoxifen in reversing DMD signatures given available dosing regimens. Additionally, pathway-level insights support endoxifen activation of myogenesis, oxidative phosphorylation, estrogen receptor beta (ERβ) activation, and inhibition of pro-inflammatory and epithelial-to-mesenchymal transition (EMT) pathways in DMD. These findings suggest (Z)-endoxifen may act on utrophin-linked regulatory axes, thereby potentially contributing to functional compensation for dystrophin deficiency. This provides justification for endoxifen's development as a mutation-agnostic DMD therapeutic approach.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"574524"},"PeriodicalIF":9.9,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agreement and Comparative Performance of Cognitive Testing, Visual MRI Rating, and Automated Brain Morphometry in Older Adults with Suspected Dementia in Uganda.","authors":"Rita Nassanga, Mark Kaddumukasa, Stephen E Jones, Martha Sajatovic, Ajay Nemani, Roy Clark Basiimwa, Michael Grace Kawooya, James K Tumwine, Kamada Lwere, Joy Louise Gumikiriza-Onoria, Aloysius Gonzaga Mubuuke, Noeline Nakasujja","doi":"10.2147/DNND.S590989","DOIUrl":"10.2147/DNND.S590989","url":null,"abstract":"<p><strong>Background: </strong>Dementia diagnosis in sub-Saharan Africa is constrained by limited access to specialist neuroimaging interpretation and reduced specificity of brief cognitive tools in low-literacy populations. We evaluated the agreement, incremental value, and comparative performance of Mini Mental State Exam (MMSE), visual MRI medial temporal atrophy (MTA), and automated brain morphometry in older Ugandan adults with suspected dementia.</p><p><strong>Methods: </strong>In this cross-sectional study, adults aged ≥50 years with suspected dementia were recruited from neurology and psychiatry clinics at two hospitals and from a community cohort. Participants underwent MMSE and standardized 1.5T brain MRI. Visual MRI ratings were performed by radiologists blinded to clinical data, and automated morphometry was generated using NeuroQuant^® normative percentiles. Hippocampal occupancy (HOC <5th percentile) was used as a reference MRI biomarker for comparative classification. Agreement between visual and automated measures was assessed using Spearman correlation and intraclass correlation. Incremental value was assessed using regression models, and comparative performance using area under the curve (AUC).</p><p><strong>Results: </strong>Sixty-three participants were included (mean age 75.6 ± 8.7 years; 49 female). Agreement between visual ratings and automated morphometry was poor. MMSE correlated inversely with MTA (<i>ρ</i> = -0.47; p = 0.049) and correlated positively with hippocampal volume percentile (<i>ρ</i> = 0.46; p = 0.056). Adding hippocampal volume to MTA did not improve model fit for MMSE (ΔR² = 0.028; p = 0.18). For comparative classification, MMSE alone was sensitive but poorly specific, while the combined MMSE-MTA model improved specificity and discrimination (AUC 0.70 vs 0.62 for either measure alone).</p><p><strong>Conclusion: </strong>Visual and automated MRI measures were not interchangeable in this heterogeneous cohort. Automated hippocampal volumetry added limited value beyond visual MTA for global cognition, while combining MMSE with visual MTA showed modest improvement in comparative classification and warrants further validation.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"590989"},"PeriodicalIF":9.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism.","authors":"Tunan Ding, Junlei Chen, Yunsheng Xiang, Xiaojie Zhou, Hongbo Zheng, Yihan Bai, Weihao Wang, Qiang Fu, Yan Chen, Yin Fu","doi":"10.2147/DNND.S580890","DOIUrl":"10.2147/DNND.S580890","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify novel therapeutic targets for Alzheimer's disease (AD) by investigating the role of the intestinal flora (IF) via the gut-brain axis, and to predict a potential natural compound for AD treatment and elucidate its underlying mechanism.</p><p><strong>Methods: </strong>Following a primary analytical axis, we first employed Mendelian randomization (MR) to infer causal relationships between gut microbiota and AD. To pinpoint molecular targets, we integrated Summary-data-based MR (SMR) with single-cell and spatial transcriptomics. Subsequently, network pharmacology and molecular docking were used to identify stigmasterol as a candidate compound targeting the causal pathway. Finally, the neuroprotective effects and the STIM1/Orai1-mediated mechanism were experimentally validated in vitro using Aβ_1-42 exposed SH-SY5Y cells.</p><p><strong>Results: </strong>MR-based causal inference identified Desulfovibrio as a risk factor for AD, while Slackia and the Lachnospiraceae NK4A136 group were protective factors. Seven key AD-related genes were identified by combining MR results with databases, which were highly druggable. SMR analysis and multi-omics integration pinpointed STIM1-mediated calcium signaling as the core causal pathway. Following the identification of stigmasterol via network pharmacology and molecular docking, in vitro experimental validation confirmed that stigmasterol significantly inhibited Aβ_1-42 induced neuronal apoptosis and calcium overload by specifically modulating the STIM1/Orai1 pathway and the Bcl-2/Bax ratio.</p><p><strong>Conclusion: </strong>This study decodes the gut-brain axis by establishing the specific causal pathway. We demonstrate that Stigmasterol exerts neuroprotective effects by inhibiting apoptosis through a IF-associated mechanism involving the STIM1/Orai1 pathway, provideing novel insights into AD pathogenesis and offering a promising therapeutic strategy based on natural compounds.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"580890"},"PeriodicalIF":9.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Siponimod with Up to 2 Years of Treatment in a Real-World Setting in People with SPMS: Analysis from the Novartis Global Managed Access Program.","authors":"Antonio Carotenuto, Dimitris Naoumis, Vincenzo Brescia Morra, Evangelos Kouremenos, Suzannah Hetherington, Sophie Arnould, Virginia de Las Heras","doi":"10.2147/DNND.S540207","DOIUrl":"10.2147/DNND.S540207","url":null,"abstract":"<p><strong>Background: </strong>Limited real-world data exist on the effectiveness of siponimod in people living with secondary progressive multiple sclerosis (plwSPMS).</p><p><strong>Objective: </strong>To analyze the real-world data of patients receiving siponimod under a managed access program (MAP).</p><p><strong>Methods: </strong>The MAP was implemented in countries where siponimod was not approved and provision via MAP was permitted under local regulations. Data on the demographic/clinical characteristics and clinical outcomes of the cohort included in this MAP between February 2019 and April 2022, were collected from physicians using a Novartis database.</p><p><strong>Results: </strong>Among patients with evidence of starting siponimod treatment in the MAP (n=516), the mean EDSS at baseline was 5.2. Among those with post-baseline data available (n=423), the mean change from baseline in EDSS score at month 6 was -0.04 (95% confidence interval [CI]: -0.10, 0.01) and 0.03 (95% CI: -0.03, 0.10) at month 24), and the annual relapse rate was 0.023. Cognition was stable or improved in patients for whom data was available. Among patients with ≥1 MRI assessment (n=165), 154 (93.3%) had no findings of disease activity.</p><p><strong>Conclusion: </strong>This real-world data set analysis provides data on the demographic/clinical characteristics of plwSPMS taking siponimod in clinical practice under MAP criteria and on the effectiveness that can be attained.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"540207"},"PeriodicalIF":9.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emodin, a Phytotherapeutic Anthraquinone, Potently Attenuates Synaptic Redox Pathology in Aged Rats.","authors":"Priyanka Saha, Faraz Ahmad","doi":"10.2147/DNND.S570320","DOIUrl":"10.2147/DNND.S570320","url":null,"abstract":"<p><strong>Background: </strong>Aging is associated with increased oxidative stress, which leads to synaptic vulnerability and psychiatric and cognitive deficits. Maintaining redox homeostasis is crucial for synaptic health. However, age-related alterations in synapse-specific antioxidant capacity remain poorly understood. Moreover, effective therapeutic strategies to counteract these changes are lacking. This study aimed to assess redox parameters in ex vivo synaptic terminals from young and old rat brains and evaluate the modulatory effects of the phytotherapeutic compound emodin.</p><p><strong>Methods: </strong>Brain synaptosomes were isolated from young and old male Wistar rats. The antioxidant capacities were determined using 2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid] (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Oxidative stress and damage were assessed by quantifying reactive oxygen species (ROS) and nitrogen species (RNS) and examining oxidative modifications of proteins and lipids. The antioxidant effects of emodin were investigated in mitigating synaptic oxidative stress and damage.</p><p><strong>Results: </strong>A significant decline in antioxidant capacity and increase in ROS levels were observed in the synaptosomes of aged animals. Oxidative damage was also evident as increased protein carbonylation, thiol oxidation, and lipid peroxidation. Emodin treatment improved redox balance by reducing ROS levels, decreasing oxidative damage markers, and enhancing antioxidant defenses, particularly in older animals.</p><p><strong>Conclusion: </strong>Aging disrupts synaptic redox homeostasis and increases the susceptibility to oxidative damage. Emodin exerts protective antioxidant effects by mitigating oxidative stress and enhancing the redox capacity of the synaptosomes. These findings suggest that emodin may have therapeutic potential in preserving synaptic function under conditions of age-related oxidative stress, although further functional and molecular studies are warranted to validate its neuroprotective efficacy.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"570320"},"PeriodicalIF":9.9,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Spectrum and Phenotypic Variability in Chinese Patients with Multisystem Proteinopathy and Related Disorders.","authors":"Xingyu Xia, Xi Chen, Yiming Sun, Ming Zhang, Kai Qiao, Yan Chen, Chongbo Zhao, Yi Dong, Wenhua Zhu","doi":"10.2147/DNND.S568971","DOIUrl":"10.2147/DNND.S568971","url":null,"abstract":"<p><strong>Objective: </strong>Multisystem proteinopathy (MSP) is a pleiotropic group of disorders initially presenting as inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and/or Paget disease of bone (PDB). Additional genes including <i>MATR3, OPTN</i>, and <i>ANXA11</i>, have recently been implicated in MSP-like disorders, further expanding the genetic spectrum. This research aims to study the genetic and clinical characteristics of MSP and related disorders in a large Chinese cohort.</p><p><strong>Methods: </strong>Twenty-nine patients were identified in 953 patients diagnosed with ALS, IBM, or dementia at Huashan Hospital between 2000 and 2024. Variants in MSP-related genes were detected using next-generation sequencing and confirmed by Sanger sequencing. Clinical, pathological, imaging, and electromyography data were collected and analyzed.</p><p><strong>Results: </strong>A total of 29 patients (3.0%) were identified as carrying MSP-related gene variants. Most patients were male (72.4%), with disease onset predominantly in the third to fifth decades of life. The majority of patients (21/29) presented with a single clinical phenotype. ALS was the most common phenotype (20/29), followed by IBM (10/29), FTD (7/29), and PDB (1/29). The most frequent variants were in <i>ANXA11</i> (34.5%) and <i>VCP</i> (20.7%), followed by <i>OPTN</i> (17.2%),<i> SQSTM1</i> (10.3%), <i>MATR3</i> (10.3%), and <i>HNRNPA1</i> (6.9%). All patients with <i>VCP</i> variants presented with initial lower limb involvement, whereas those carrying <i>ANXA11</i> or <i>OPTN</i> variants predominantly showed upper limb or bulbar onset. Patients harboring <i>OPTN</i> variants had a later age at onset compared with those carrying <i>VCP</i> or <i>MATR3</i> variants. Patients with ALS-onset exhibited faster progression compared with those with myopathy-onset, even when harboring identical variants.</p><p><strong>Conclusion: </strong>This study broadens the clinical and genetic landscape of MSP and related disorders in a Chinese cohort. These results emphasize the clinical utility of next-generation sequencing for improving diagnostic accuracy in patients with unexplained neuromuscular or cognitive presentations, especially in the presence of multisystem involvement.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"568971"},"PeriodicalIF":9.9,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Therapy for Alzheimer's Disease Based on the Cerebral Lymphatic System.","authors":"Feiyue Mi, Li Ren, Dongfeng Pan, Changyin Yu","doi":"10.2147/DNND.S574901","DOIUrl":"10.2147/DNND.S574901","url":null,"abstract":"<p><strong>Background: </strong>Conventional therapeutic interventions for Alzheimer's disease (AD) are limited by multiple drawbacks, including anticholinesterase inhibitors, glutamate receptor antagonists, intestinal flora regulators and Aβ-targeting monoclonal antibodies, which only achieve modest symptomatic relief, are accompanied by notable adverse events (e.g., intracerebral hemorrhage, cerebral edema) and have suboptimal clinical efficacy. In recent years, the cerebral lymphatic system, consisting of the glial lymphatic system (GLS) and meningeal lymphatic vessels (MLVs), has been identified as a key mediator of amyloid β-protein (Aβ) clearance and a critical driver of AD pathogenesis. Lymphatic dysfunction in this system precedes and exacerbates Aβ deposition and cognitive decline in AD patients, revealing the close association between cerebral lymphatic system impairment and AD progression.</p><p><strong>Purpose: </strong>This study aims to focus on the emerging therapeutic advancements for AD targeting the cerebral lymphatic system, moving beyond the conventional symptomatic treatments and Aβ-centric interventions. It also intends to systematically summarize the relevant mechanisms of the cerebral lymphatic system in AD and the diverse therapeutic strategies targeting this system, thus providing a framework for developing innovative clinical interventions for AD.</p><p><strong>Methods: </strong>This study adopted a review approach, systematically collating and analyzing existing research on the cerebral lymphatic system and AD, including the cerebral lymphatic pathway of Aβ clearance, the pathological consequences of lymphatic impairment in AD, and various therapeutic strategies targeting the cerebral lymphatic system that have been reported in current studies.</p><p><strong>Results: </strong>The review identified and summarized multiple categories of effective therapeutic strategies targeting the cerebral lymphatic system for AD, covering pharmacological agents (VEGF-C, traditional Chinese medicines, oxytocin), photobiotherapies (808 nm near-infrared light, 40 Hz multisensory stimulation), physiotherapies (aerobic exercise, rTMS), gene therapy (DSCR1 upregulation), and surgical interventions (lymphatic-venous anastomosis). All these strategies are designed to optimize cerebral lymphatic function and thereby enhance Aβ drainage in the brain.</p><p><strong>Conclusion: </strong>Optimizing cerebral lymphatic function to enhance Aβ drainage is a viable, disease-modifying therapeutic direction for AD. This therapeutic approach targeting the cerebral lymphatic system can serve as a complementary or alternative method to current symptomatic or Aβ-targeted treatments for AD, and also provides a theoretical and practical framework for the development of innovative clinical interventions for the disease.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"16 ","pages":"574901"},"PeriodicalIF":9.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}