Jana Kleinerova, Giorgia Querin, Pierre-Francois Pradat, We Fong Siah, Peter Bede
{"title":"New developments in imaging in ALS.","authors":"Jana Kleinerova, Giorgia Querin, Pierre-Francois Pradat, We Fong Siah, Peter Bede","doi":"10.1007/s00415-025-13143-8","DOIUrl":"10.1007/s00415-025-13143-8","url":null,"abstract":"<p><p>Neuroimaging in ALS has contributed considerable academic insights in recent years demonstrating genotype-specific topological changes decades before phenoconversion and characterising longitudinal propagation patterns in specific phenotypes. It has elucidated the radiological underpinnings of specific clinical phenomena such as pseudobulbar affect, apathy, behavioural change, spasticity, and language deficits. Academic concepts such as sexual dimorphism, motor reserve, cognitive reserve, adaptive changes, connectivity-based propagation, pathological stages, and compensatory mechanisms have also been evaluated by imaging. The underpinnings of extra-motor manifestations such as cerebellar, sensory, extrapyramidal and cognitive symptoms have been studied by purpose-designed imaging protocols. Clustering approaches have been implemented to uncover radiologically distinct disease subtypes and machine-learning models have been piloted to accurately classify individual patients into relevant diagnostic, phenotypic, and prognostic categories. Prediction models have been developed for survival in symptomatic patients and phenoconversion in asymptomatic mutation carriers. A range of novel imaging modalities have been implemented and 7 Tesla MRI platforms are increasingly being used in ALS studies. Non-ALS MND conditions, such as PLS, SBMA, and SMA, are now also being increasingly studied by quantitative neuroimaging approaches. A unifying theme of recent imaging papers is the departure from describing focal brain changes to focusing on dynamic structural and functional connectivity alterations. Progressive cortico-cortical, cortico-basal, cortico-cerebellar, cortico-bulbar, and cortico-spinal disconnection has been consistently demonstrated by recent studies and recognised as the primary driver of clinical decline. These studies have led the reconceptualisation of ALS as a \"network\" or \"circuitry disease\".</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"392"},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria A Rocca, Sophia Ratzinger, Paolo Preziosa, Alessandro Meani, Mor Gueye, Paolo Vezzulli, Elisabetta Pagani, Federica Esposito, Antonino Giordano, Bruno Colombo, Andrea Falini, Massimo Filippi
{"title":"Clinical integration of brain and cord MRI features improves differential diagnosis of multiple sclerosis.","authors":"Maria A Rocca, Sophia Ratzinger, Paolo Preziosa, Alessandro Meani, Mor Gueye, Paolo Vezzulli, Elisabetta Pagani, Federica Esposito, Antonino Giordano, Bruno Colombo, Andrea Falini, Massimo Filippi","doi":"10.1007/s00415-025-13124-x","DOIUrl":"10.1007/s00415-025-13124-x","url":null,"abstract":"<p><strong>Objective: </strong>To explore the role of brain and spinal cord MRI features in differentiating patients with suspected central nervous system (CNS) inflammatory diseases.</p><p><strong>Material and methods: </strong>Prospective data from 125 patients undergoing diagnostic evaluation, including 1.5 T brain and spinal cord MRI scans from February 2021 and March 2024 were analyzed. The cohort comprised 91 patients with multiple sclerosis (MS), 15 with other inflammatory neurological diseases (OIND), and 19 with non-inflammatory neurological diseases (NIND). Brain and spinal cord lesion topographies and morphological features were evaluated to identify MRI features discriminating MS from OIND and NIND.</p><p><strong>Results: </strong>Random forest analysis identified key MRI features supporting MS diagnosis over OIND: absence of longitudinally extensive transverse myelitis (relative importance [RI] = 100%), presence of ≥ 1 Dawson's finger (RI = 55.3%), ≥ 1 cortical lesion (RI = 42.6%), and ≥ 1 brain T2-hyperintense white matter (WM) lesion (RI = 36.4%). After excluding the presence of ≥ 1 brain T2-hyperintense WM lesion, fulfilling ≥ 2 of the 3 selected criteria distinguished MS from OIND patients with a sensitivity of 0.59 and a specificity of 0.80. For distinguishing MS from NIND, relevant MRI features included ≥ 1 T2-hyperintense spinal cord lesion (RI = 100.0%), ≥ 1 Dawson's finger (RI = 84.3%), ≥ 1 cortical lesion (RI = 61.4%), ≥ 1 cerebellar peduncle lesion (RI = 52.2%) and ≥ 3 central vein sign-positive lesions (RI = 27.8%). Fulfilling ≥ 2 of the 5 selected criteria identified MS patients with a sensitivity of 0.64 and a specificity of 0.84.</p><p><strong>Conclusion: </strong>Integrating specific MRI features in the diagnostic work-up of patients with suspected CNS inflammatory disease improves differentiation between MS, OIND, and NIND, reducing the risk of misdiagnosis.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"388"},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Gardoni, Elisabetta Sarasso, Silvia Basaia, Davide Corbetta, Lucia Zenere, Andrea Grassi, Elisa Canu, Veronica Castelnovo, Elisa Sibilla, Massimo Malcangi, Roberta Balestrino, Daniele Emedoli, Maria Antonietta Volontè, Massimo Filippi, Federica Agosta
{"title":"Handwriting, touchscreen dexterity and bradykinesia measures in Parkinson's disease: a feature selection study.","authors":"Andrea Gardoni, Elisabetta Sarasso, Silvia Basaia, Davide Corbetta, Lucia Zenere, Andrea Grassi, Elisa Canu, Veronica Castelnovo, Elisa Sibilla, Massimo Malcangi, Roberta Balestrino, Daniele Emedoli, Maria Antonietta Volontè, Massimo Filippi, Federica Agosta","doi":"10.1007/s00415-025-13121-0","DOIUrl":"10.1007/s00415-025-13121-0","url":null,"abstract":"<p><strong>Introduction: </strong>Bradykinesia affects handwriting and smartphone usage in patients with Parkinson's disease (pwPD).</p><p><strong>Objective: </strong>To assess handwriting, hand dexterity, smartphone usage, and bradykinesia in pwPD and identify features that best describe upper-limb alterations in pwPD.</p><p><strong>Methods: </strong>Forty pwPD and 30 age/sex-matched healthy controls were included. We used standard handwriting/dexterity tests: Manual-Ability-Measure-36, Purdue-Pegboard-Test (PPT) and copy of a text on paper. Spatiotemporal handwriting parameters were assessed using tests on a tablet: copy of text and pre-writing tasks. To obtain objective data on movement speed and amplitude on the smartphone, we developed tests involving the most commonly used gestures (tap, swipe, and slide). Bradykinesia during a finger-tapping task was evaluated using electromagnetic sensors. Sequential feature selection models were used to identify the parameters best distinguishing pwPD and healthy controls.</p><p><strong>Results: </strong>PwPD relative to healthy controls showed reduced manual ability and dexterity. They showed reduced movement amplitude and speed in smartphone tests and signs of micrographia during handwriting tests. Moreover, kinematic parameters correlated with both PPT and Movement Disorder Society-Unified Parkinson's Disease Rating Scale III. Each feature selection model demonstrated a good accuracy, particularly when including standard handwriting/dexterity tests (R<sup>2</sup> = 0.90), tests on smartphone (R<sup>2</sup> = 0.94) and all the features together (R<sup>2</sup> = 0.97). The best features were self-reported manual abilities, PPT, tap and swipe speed/amplitude on smartphone.</p><p><strong>Conclusions: </strong>This study showed that technological assessments can be added to standard evaluations to provide quantitative measures of handwriting, dexterity, and bradykinesia that will be useful to assess PD progression and the effects of interventions in pwPD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"389"},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Liu, Kun Zhang, Anquan Hu, Yumeng Li, Heyan Qin, Wei Sun, Xian Li, Feng Chen, Tao Liu
{"title":"Global burden of motor neuron disease: unraveling socioeconomic disparities, aging dynamics, and divergent future trajectories (1990-2040).","authors":"Kai Liu, Kun Zhang, Anquan Hu, Yumeng Li, Heyan Qin, Wei Sun, Xian Li, Feng Chen, Tao Liu","doi":"10.1007/s00415-025-13130-z","DOIUrl":"10.1007/s00415-025-13130-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Motor neuron disease (MND) is a progressive neurodegenerative disorder associated with high morbidity and mortality. With global aging, the burden of MND is expected to increase, particularly in regions with rapidly aging populations. This study utilizes Global Burden of Disease (GBD) 2021 data to assess the global and regional MND burden from 1990 to 2021, examining trends by age, sex, and socio-demographic index (SDI), and projecting future trends to 2040.</p><p><strong>Methods: </strong>Data from the GBD 2021 database for the years 1990-2021 were analyzed to evaluate age-standardized prevalence rates (ASPR), incidence rates (ASIR), mortality rates (ASMR), and disability-adjusted life years (DALYs) for MND across SDI regions, age groups, and sexes. Temporal trends were explored using joinpoint regression analysis, while future projections were generated using the Bayesian age-period-cohort (BAPC) model for 2021-2040.</p><p><strong>Results: </strong>From 1990 to 2021, global MND prevalence increased by 68.43%, reaching 272,732 cases, while the age-standardized prevalence rate (ASPR) slightly declined, reflecting the influence of population aging. Although global incidence increased by 74.54%, the age-standardized incidence rate (ASIR) showed a modest decline, suggesting improvements in diagnostic practices. Mortality and DALY rates continued to rise globally, with high-SDI regions bearing the highest burden. Projections indicate that by 2040, global MND prevalence will decline slightly, while incidence, mortality, and DALYs will continue to rise in low- and middle-SDI regions due to aging populations.</p><p><strong>Discussion: </strong>The global MND burden is heavily influenced by aging, particularly in high-SDI regions. Although incidence rates have slightly decreased, mortality and disability burdens are increasing, highlighting ongoing challenges in disease management and treatment. The findings stress the importance of age-targeted interventions, improving healthcare access, and addressing socio-economic disparities to mitigate the future impact of MND, particularly in low- and middle-SDI regions.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"390"},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalie Berger, Diether Kramer, Michael Schrempf, Edith Hofer, Alexander Pichler, Simon Fandler-Höfler, Melanie Haidegger, Isra Hatab, Martin Heine, Jan Jagiello, Herbert Koller, Stefan Lilek, Sai Veeranki, Christian Enzinger, Thomas Gattringer, Markus Kneihsl
{"title":"Predicting delirium in acute ischemic stroke: the PREDELIS score.","authors":"Natalie Berger, Diether Kramer, Michael Schrempf, Edith Hofer, Alexander Pichler, Simon Fandler-Höfler, Melanie Haidegger, Isra Hatab, Martin Heine, Jan Jagiello, Herbert Koller, Stefan Lilek, Sai Veeranki, Christian Enzinger, Thomas Gattringer, Markus Kneihsl","doi":"10.1007/s00415-025-13073-5","DOIUrl":"10.1007/s00415-025-13073-5","url":null,"abstract":"<p><strong>Background: </strong>Delirium, defined as an acute, fluctuating disturbance in consciousness, attention and cognition, is a common stroke complication and associated with poor functional outcome. Although resource-intensive prevention strategies could reduce delirium rates, their implementation in unselected stroke patients is challenging. This study aimed to develop a risk score for predicting delirium in acute ischemic stroke (PREDELIS).</p><p><strong>Methods: </strong>We retrospectively included all ischemic stroke patients admitted to five stroke units of Styria, Austria, between 2013 and 2021. Data were retrieved from a comprehensive medical information system using semi-automated data extraction. The PREDELIS score was based on multivariable logistic regression analysis to identify admission variables associated with delirium.</p><p><strong>Results: </strong>14,475 acute ischemic stroke patients (median age: 76 years, 46% women) were split in a 40% derivation (n = 6151; delirium = 398, 6.5%) and a 60% validation cohort (n = 8324; delirium: 568, 6.8%). Previous delirium (4 points), chronic alcohol consumption (3), age > 70 years (2), male sex (2), infection (2), admission NIHSS > 7 (1), non-lacunar stroke (1) and vision/hearing impairment (1) were associated with delirium (all p < 0.05) and included in our score (median: 5 points). The score´s area under the curve was 0.72 in both the derivation (95% CI 0.69-0.75) and the validation cohort (95% CI 0.70-0.74). While patients with a score of ≤ 5 had a low delirium risk (2.5%), a score of ≥ 9 indicated a high risk (30.9%).</p><p><strong>Discussion and conclusion: </strong>This study introduces a novel score for early delirium risk estimation in ischemic stroke patients, aiding clinicians in identifying high-risk individuals for targeted screening and prevention.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"391"},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shengfei Hu, Ziyu Liao, Rui Wang, Milan Zhang, Qiuming Zeng, Zhihua Zhao, Xi Wang, Hongyu Zhou, Wei Li, Yaxin Lu, Huan Yang, Wei Qiu, Rui Li
{"title":"Relapse risk after rituximab discontinuation in neuromyelitis optica spectrum disorders: a multi-center retrospective cohort study.","authors":"Shengfei Hu, Ziyu Liao, Rui Wang, Milan Zhang, Qiuming Zeng, Zhihua Zhao, Xi Wang, Hongyu Zhou, Wei Li, Yaxin Lu, Huan Yang, Wei Qiu, Rui Li","doi":"10.1007/s00415-025-13125-w","DOIUrl":"10.1007/s00415-025-13125-w","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate the association between rituximab (RTX) treatment duration and relapse risk, and explore clinical outcomes following treatment discontinuation in neuromyelitis optica spectrum disorder (NMOSD).</p><p><strong>Methods: </strong>We retrospectively collected data from rituximab-treated patients (>1-year follow-up after treatment initiation) with NMOSD at five major clinical centers in China between 2016 and 2023. The main outcome measures were changes in relapse risk based on the RTX treatment duration and clinical outcomes following relapse after RTX discontinuation. The Andersen-Gill model was used to analyze treatment duration-relapse risk associations.</p><p><strong>Results: </strong>In total, 106 rituximab-treated patients were included (40 patients discontinued and 66 continued RTX). Longer RTX treatment significantly reduced relapse risk (hazard ratio [HR]=0.43, P < 0.001). Among 28 patients who discontinued RTX and were followed-up for >1 year after drug withdrawal, 53.6% (15/28) relapsed at a median interval of 14 months. Patients with >2 years of RTX treatment exhibited lower annual relapse rate (ARR) (mean ARR: 0.97 vs. 0.28, P = 0.020) and less severe relapses (mean ΔEDSS score: 1.42 vs. 0.50, P = 0.021) after discontinuation, compared to pre-treatment levels. Only one of four (25%) longer-treated and clinically stable patients (≥2 years of RTX treatment and no relapses ≥2 years before discontinuation) experienced a non-severe relapse by 50 months. Patients aged >55 years in the discontinuation group had the lowest post-discontinuation relapse rate.</p><p><strong>Interpretation: </strong>RTX treatment duration strongly correlated with reduced relapse risk in NMOSD patients. Relapse risk after RTX discontinuation was lower than that after discontinuing traditional oral immunosuppressants, particularly in patients with longer treatment and clinical stability.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"387"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safety and efficacy of teriflunomide on clinical course, and laboratory findings in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis: a triple-blind study.","authors":"Neda Ghadiri Jozan, Zohreh Vahidi, Houshang Rafatpanah, Reza Boostani, Fariba Zemorshidi, Mohammadali Sahraian, Jamshid Tabeshpour, Mahdieh Baghaei, Mohammadali Nahayati","doi":"10.1007/s00415-025-13134-9","DOIUrl":"10.1007/s00415-025-13134-9","url":null,"abstract":"<p><strong>Background: </strong>HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS). Teriflunomide is an oral agent developed for the treatment of multiple sclerosis (MS) by suppressing the proliferation of autoreactive lymphocytes. This study was conducted to evaluate the efficacy of teriflunomide in HAM/TSP patients in Northeast Iran.</p><p><strong>Methods: </strong>This study was a triple-blind, randomized, placebo-controlled trial involving 22 patients with HAM/TSP. The intervention group (n = 11) received one tablet of teriflunomide (14 mg daily), while the control group (n = 11) received one placebo tablet for 12 months. Muscle strength, spasticity, motor disability, urinary disorders, walking speed, laboratory factors, and drug complications were examined during the study.</p><p><strong>Results: </strong>In the intervention group, consumption of teriflunomide decreased the duration of walking according to the T25FW test (p = 0.01). The severity of OMDS disability also significantly decreased (P < 0.001). Additionally, the total score of UDS in the intervention group decreased. The levels of HTLV-1 proviral load significantly decreased (p = 0.003). No adverse effects were observed, and the increase in liver enzyme levels was tolerable and controllable.</p><p><strong>Conclusions: </strong>Teriflunomide effectively reduced the proviral load, improved the severity of disability and walking speed, and better controlled urinary and constipation symptoms without any adverse effects. Therefore, teriflunomide can be considered a disease-modifying therapy for patients with HAM/TSP. However, further studies with a large number of patients and longer duration, along with the determination of specific HAM/TSP-associated biomarkers, are needed to validate the results of the present study.</p><p><strong>Trial registration: </strong>IRCT20180618040127N3; November 19, 2021.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"386"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Randomized controlled trials for multiple sclerosis: integrating pathology-driven outcomes to capture therapeutic efficacy.","authors":"Massimo Filippi, Paolo Preziosa, Maria A Rocca","doi":"10.1007/s00415-025-13141-w","DOIUrl":"10.1007/s00415-025-13141-w","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"385"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junying Li, Dan Yang, Rui Song, Jian Wang, Lanying He
{"title":"Correction: The impact of white matter hyperintensities on short-term outcomes of reperfusion therapy in patients with acute ischemic stroke.","authors":"Junying Li, Dan Yang, Rui Song, Jian Wang, Lanying He","doi":"10.1007/s00415-025-12956-x","DOIUrl":"10.1007/s00415-025-12956-x","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"384"},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel strategies for targeting tau oligomers in neurodegenerative diseases.","authors":"Jing Lin, Hong Li, Lingxia Jiang, Jian Li","doi":"10.1007/s00415-025-13117-w","DOIUrl":"10.1007/s00415-025-13117-w","url":null,"abstract":"<p><p>Tau protein is a soluble microtubule-associated protein enriched in neurons, is mainly distributed in the central nervous system, and is responsible for stabilizing neurons. Tau maintains nerve cell morphology and internal transport by binding to normal microtubules. In neurodegenerative diseases, such as Alzheimer's disease (AD), tau proteins undergo aberrant phosphorylation, resulting in their removal from microtubules and the formation of neurofibrillary tangles (NFTs), which are key pathological features. In contrast to the late formation of non-soluble NFTs, early, smaller, soluble tau oligomers (tauO) with disseminated toxicity are considered necessary in neurodegenerative disorders, such as the primary form of tau toxicity in the AD process. Although an increasing number of studies are focusing on tauO, there are still problems to be solved, mainly concerning the molecular and inhibitory mechanisms of tauO toxicity. In this paper, we summarize the new strategies for the molecular mechanisms of tauO toxicity, detection methods, and interventions in the last five years. An outlook on these new strategies and the challenges that may be foreseen is presented to provide new directions for future applications in the clinical treatment of neurodegenerative diseases.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"383"},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}