Annals of Neurology最新文献

{"title":"Salivary Dim-Light Melatonin Onset is Associated with Functional Decline, Respiratory Symptom Emergence, and Survival in Early Amyotrophic Lateral Sclerosis.","authors":"Alessandro Bombaci, Antonella Iadarola, Alessia Giraudo, Elisa Fattori, Serena Sinagra, Alice Magnino, Maria Falbo, Giovanni De Marco, Andrea Calvo, Adriano Chiò, Alessandro Cicolin","doi":"10.1002/ana.78398","DOIUrl":"https://doi.org/10.1002/ana.78398","url":null,"abstract":"<p><strong>Objective: </strong>Sleep-wake and circadian disturbances are increasingly recognized in people living with amyotrophic lateral sclerosis (plwALS), but endogenous circadian phase timing and its prognostic significance in early disease remain unclear. We assessed whether salivary dim-light melatonin onset (DLMO), an objective marker of central circadian phase, is altered in early plwALS and whether it provides prognostic information.</p><p><strong>Methods: </strong>In this prospective longitudinal observational study, plwALS within 18 months of symptom onset underwent home-based salivary melatonin sampling under dim-light conditions at 6 predefined time points around habitual sleep onset. Melatonin profiles were modeled using cubic smoothing splines, and DLMO was defined when the fitted curve first reached 3 pg/ml. Clinical, respiratory, and sleep assessments were collected at baseline (T0) and after 6 months (T6); a subgroup repeated saliva sampling at T6. Age- and sex-matched controls underwent melatonin profiling. Associations with disease progression, incident respiratory symptoms, and survival/tracheostomy were examined using regressions and survival analyses.</p><p><strong>Results: </strong>A total of 50 plwALS were enrolled. Compared with controls, plwALS showed an earlier DLMO (20:24 ± 1:18 vs 20:58 ± 0:50; p = 0.028) despite similar habitual sleep onset and chronotype. Within ALS cohort, a later baseline DLMO correlated with worse functional/motor status, faster progression of disease, incident dyspnea/orthopnea by T6 (adjusted OR 3.11; p = 0.019), and poorer survival/tracheostomy-free outcome. In the resampled subgroup (n = 28), DLMO and melatonin-derived metrics did not change over ~6 months.</p><p><strong>Interpretation: </strong>Circadian phase alterations are detectable in early ALS. Baseline DLMO showed exploratory associations with functional, respiratory, and survival outcomes. Larger independent cohorts are required before DLMO can be considered a validated prognostic biomarker. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated Fibroblast Imaging in Baló's Concentric Sclerosis.","authors":"Amélie Castiaux, Sophie Elands, Xavier De Tiège, Gil Leurquin-Sterk","doi":"10.1002/ana.78399","DOIUrl":"https://doi.org/10.1002/ana.78399","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting Hyperacute IL-1β and NET Signals in Large-Vessel Occlusion Stroke.","authors":"Xiaohui Sun, Zhuoma Pengmao, Lu Xu, Couronne Adoummadji Benaindo, Xinyue Wang, Ceshu Gao, Jian Wu","doi":"10.1002/ana.78372","DOIUrl":"https://doi.org/10.1002/ana.78372","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Interpreting Hyperacute IL-1β and NET Signals in Large-Vessel Occlusion Stroke\".","authors":"Justine Münsterberg, Tim Magnus, Mathias Gelderblom","doi":"10.1002/ana.78373","DOIUrl":"https://doi.org/10.1002/ana.78373","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild Amyloid Burden in the Brains of Cognitively Unimpaired Individuals is Associated with Long-Term Cognitive Impairment.","authors":"Chengjie Xiong, Jingqin Luo, Sarah Hartz, Suzanne E Schindler, Walter Kukull, Jason Hassenstab, David A Wolk, Carey E Gleason, Sterling C Johnson, Reisa Sperling, Keith Johnson, Erik D Roberson, Krista L Moulder, Emily Gremminger, Folasade Agboola, Elizabeth A Grant, Russ Hornbeck, Parinaz Massoumzadeh, Sarah Keefe, Donna Dierker, David Holtzman, John C Morris","doi":"10.1002/ana.78392","DOIUrl":"https://doi.org/10.1002/ana.78392","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to identify the minimal amount of amyloid burden measured by positron emission tomography (PET) in amyloid-negative cognitively unimpaired individuals that predicts the development of cognitive impairment.</p><p><strong>Methods: </strong>A total of 1,896 cognitively unimpaired participants underwent longitudinal clinical/cognitive assessments for up to 20.3 years after amyloid PET imaging. Cox proportional hazards models were used to assess how the risk of cognitive impairment was associated with subthresholds of amyloid PET Centiloid. Linear mixed effects models were used to associate the longitudinal cognitive decline and amyloid accumulation with baseline amyloid burden.</p><p><strong>Results: </strong>Amyloid-positive participants (Centiloid >20; n = 421) were 154% (hazard ratio 2.54, p < 0.0001) more likely to develop cognitive impairment than amyloid-negative participants. Approximately 48.7% of the amyloid-negative participants had mild amyloid burden (defined by Centiloid from 0.93 to 20) and were 43% more likely to develop cognitive impairment (hazard ratio 1.43, p = 0.008) than the lowest amyloid group (Centiloid <0.93) approximately 10 years post baseline. Longitudinal changes in amyloid PET Centiloid and cognition followed a similar pattern: amyloid-positive participants were the fastest, followed by the mild amyloid burden group and finally the lowest amyloid group, and the cognitive trajectories for the latter 2 started to separate only approximately 10 years post baseline (p = 0.003).</p><p><strong>Interpretation: </strong>Almost half of amyloid-negative cognitively unimpaired individuals were at an elevated long-term risk of cognitive impairment, when compared with those with the lowest amyloid levels. These findings suggest that the current threshold for amyloid positivity may be overly restrictive, potentially excluding a large portion of high-risk participants from prevention trials. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemispheric Asymmetry of Neuroimaging Biomarkers in Early Onset Alzheimer's Disease: Clinical and Cognitive Outcomes.","authors":"Jacob Ziontz, Ganna Blazhenets, Adrienne Visani, Konstantinos Chiotis, Piyush Maiti, Zoe Lin, Aidyn Rose Hills, Claire Yballa, Salma Rocha, Ranjani Shankar, Virginia E Sturm, Prashanthi Vemuri, Dustin B Hammers, Ani Eloyan, Maria C Carrillo, Bradford C Dickerson, Liana G Apostolova, Gil D Rabinovici, Renaud La Joie","doi":"10.1002/ana.78391","DOIUrl":"10.1002/ana.78391","url":null,"abstract":"<p><strong>Objective: </strong>Individuals diagnosed with Alzheimer's disease (AD) often exhibit amyloid, tau, and atrophy predominantly in the left or right hemisphere, but group-level analyses typically ignore inter-individual variability and changing asymmetry patterns when averaging data across participants in phenotypically diverse cohorts.</p><p><strong>Methods: </strong>We examined left/right hemispheric asymmetry in amyloid positron emission tomography (PET), tau PET, and cortical atrophy in sporadic early-onset AD from 585 deeply phenotyped individuals across 2 cohorts to investigate its clinical correlates. For each imaging biomarker, we computed a global asymmetry index reflecting left/right hemisphere signal difference, and an analogous asymmetry value for PET/magnetic resonance imaging (MRI) voxels. We examined clinical and cognitive correlates of this asymmetry across phenotypes cross-sectionally and longitudinally in a subset of 218 participants.</p><p><strong>Results: </strong>Both left and right asymmetry were common for all clinical phenotypes and was correlated between imaging biomarkers. Asymmetry patterns varied spatially within phenotypes, and asymmetry in tau PET and MRI volumes was related to hemisphere-dependent cognitive deficits and neuropsychiatric symptoms. Longitudinal analyses revealed stable amyloid PET asymmetry, decreasing tau PET asymmetry, and increasing MRI volume asymmetry.</p><p><strong>Interpretation: </strong>Hemispheric asymmetry is common in early onset AD and correlates with clinical outcomes. Our longitudinal findings suggest a time-lagged asymmetry peak in amyloid, then tau, then atrophy. Taken together, our results position asymmetry as an important feature of AD heterogeneity, as it provides insight into disease mechanisms and trajectories. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – TOC","authors":"","doi":"10.1002/ana.78375","DOIUrl":"https://doi.org/10.1002/ana.78375","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S36","pages":"S1-S3"},"PeriodicalIF":7.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149176957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annals of Neurology: Volume 100, Number S36, October 2026","authors":"","doi":"10.1002/ana.78374","DOIUrl":"https://doi.org/10.1002/ana.78374","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S36","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149176956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"55th Child Neurology Society Annual Meeting","authors":"","doi":"10.1002/ana.78342","DOIUrl":"https://doi.org/10.1002/ana.78342","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S36","pages":"S4-S229"},"PeriodicalIF":7.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149176958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte SMN Restoration and Forskolin Treatment Improve SMA Synaptic Pathology.","authors":"Emily Welby, Xiaojie Liu, Melinda Wojtkiewicz, Linda Berg Luecke, Rebekah L Gundry, Qing-Song Liu, Allison D Ebert","doi":"10.1002/ana.78390","DOIUrl":"https://doi.org/10.1002/ana.78390","url":null,"abstract":"<p><strong>Objective: </strong>Early phenotypic presentation of central afferent synapse dysfunction within patients with spinal muscular atrophy (SMA) represents a key target for therapeutic development; however, the underlying disease mechanisms remain unresolved. By further investigating motor neuron synapse and peri-synaptic astrocyte process (PAP) defects in human SMA disease pathology, we aimed to develop a novel therapeutic approach to improve motor neuron function.</p><p><strong>Methods: </strong>We utilized healthy subjects and patients with SMA induced pluripotent stem cell (iPSC)-derived cultures to assess phenotypes occurring intrinsically within astrocyte processes (monocultures) and at the PAP-synaptic interface (co-cultures), respectively, using cell surface capture mass spectrometry proteomics, confocal and super resolution microscopy, synaptogliosome (SG) isolation, and electrophysiology.</p><p><strong>Results: </strong>SMA astrocytes demonstrated intrinsic filopodia actin defects featuring low abundance of actin-associated cell surface N-glycoproteins, decreased filopodia density and CDC42-GTP levels after actin remodeling stimulation, and significantly reduced phosphorylated ezrin, radixin, and moesin (pERM) proteins. Within the SMA motor neuron and astrocyte co-cultures, we observed concurrent decreases in synapse number, actin-associated synapsin I expression, and PAP-associated expression of pERM proteins. Our dual treatment paradigm using SMN1 gene therapy combined with forskolin treatment to stimulate actin dynamics via increasing cyclic adenosine monophosphate levels resulted in increased branching and filopodia density of SMA astrocytes, and improved synapse formation and function of SMA motor neurons.</p><p><strong>Interpretation: </strong>We define actin-associated defects impacting astrocyte filopodia dynamics and motor neuron synaptic function in SMA. This shaped our therapeutic approach targeted to SMN-dependent and actin-related disease mechanisms, which overall demonstrated improvements in motor neuron function and disease pathology. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}