Acta Neuropathologica Communications最新文献

{"title":"Amygdalar nuclei vulnerability to protein aggregates in Lewy body diseases.","authors":"Natasja A C Deshayes, Janna van Wetering, Alex Wesseling, Floris Vos, Angela Ingrassia, Yvon Galis, Laura E Jonkman, Annemieke J M Rozemuller, Wilma D J van de Berg","doi":"10.1186/s40478-026-02381-0","DOIUrl":"10.1186/s40478-026-02381-0","url":null,"abstract":"<p><p>The amygdala is highly vulnerable to protein aggregation and heavily affected in Lewy body diseases (LBDs). However, vulnerability might vary per amygdalar nucleus and it is unclear if the pattern of vulnerability across the nuclei differs between types of protein aggregation and between LBDs. In this study, we aimed to assess the vulnerability of amygdalar nuclei to multiple types of protein aggregation across LBDs. Post-mortem amygdala tissue of donors with incidental LBD (iLBD, n = 6), Parkinson's disease (PD; n = 18), dementia with Lewy bodies (DLB; n = 9) and Alzheimer's disease with Lewy bodies (AD + LB; n = 15) was immunostained with antibodies against alpha-synuclein (aSyn; EP1536Y and 5G4), amyloid beta (Aβ; 4G8), phosphorylated tau (p-tau; AT8) and phosphorylated TDP-43 (p-TDP-43; 11-9), and quantitatively analyzed using QuPath. Neuronal and astrocytic aSyn pathology were most pronounced in the parahippocampal-amygdaloid transition area (PHA) and the basal nucleus, a pattern shared by all disease groups. Vulnerability to Aβ pathology varied per group but was highest in the PHA in AD + LB, whereas diffuse plaques were most common in the accessory basal nucleus. The PHA of DLB and both the basal and accessory basal nucleus of AD + LB cases were most susceptible to p-tau pathology, with fine granular cytoplasmic neuronal tau inclusions being mostly observed in the basal nucleus and neurofibrillary tangles in the accessory basal nucleus. The nuclei in the ventromedial part of the amygdala (PHA, ventral part of the basal nucleus, and cortical nucleus) were found to be hotspots for protein aggregation across LBDs. aSyn pathology in these nuclei predominantly correlated with dementia, hallucinations and anxiety. Our results show that amygdalar nuclei vulnerability differs per protein aggregate and disease entity, although the PHA, basal nucleus and cortical nucleus are generally more vulnerable. Together, our study provides a deeper insight into the selective vulnerability of amygdalar nuclei to protein aggregates and their relation to clinical characteristics in LBDs.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534910","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}

{"title":"Correction: A rare missense variant impacting NEK1 kinase function is associated with ALS.","authors":"David Brenner, Anna Ponomarenko, Iris Petrut, Sofia Beyrle, Matilde Contardo, Isabel Loss, Constantin Radke, Jonas Frank, Eleni Zimmer, Matthias Schlesner, Pascal Achenbach, Wendy Scheveneels, Amr Aly, Hülya Nazlican, Jasper Hesebeck-Brinkmann, Patrick Oeckl, Kathrin Müller, Reiner Siebert, Tobias Böckers, Kristel van Eijk, Jan Veldink, Alexander Kleger, Medhanie Mulaw, Peter M Andersen, Karin Forsberg, Jochen H Weishaupt, Seyed Babak Loghmani, Thorsten Grehl, Philip van Damme, Joachim Weis, Alberto Catanese","doi":"10.1186/s40478-026-02380-1","DOIUrl":"10.1186/s40478-026-02380-1","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"14 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534837","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}

{"title":"Multi-omics characterization of IDH-mutant astrocytoma-derived cell lines reveals NOTCH-regulated plastic quiescent astrocyte-like state and insights into progression.","authors":"Leonor Garcia, Christine Granotier-Beckers, Donovan Pineau, Dassou Sika, Szimonetta Hideg, Camille Labadie, Kasandra Aguilar Cázarez, Jigna Kundnani, Lucille Stuani, Laurent R Gauthier, François D Boussin, Marc-André Mouthon, Serge Urbach, Khadija El Koulali, Martial Séveno, Chantal Ripoll, Kawtar Daddi, Maité Verreault, Ahmed Idbaih, Samantha O'Connor, Christopher L Plaisier, Wei Chen, Sheng-Qing Lv, Lei Zhang, Min Zheng, Valérie Rigau, Hugues Duffau, Jean-Philippe Hugnot","doi":"10.1186/s40478-026-02316-9","DOIUrl":"https://doi.org/10.1186/s40478-026-02316-9","url":null,"abstract":"<p><p>Diffuse IDH-mutant astrocytomas are brain tumors typically diagnosed as low-grade but capable of progressing to higher grades. They exhibit three cellular states resembling astrocytes, oligodendrocytes, and neural progenitor (NPC) cells. Understanding their biology has been limited by the scarcity of relevant in vitro models. Here, we established and extensively characterized four astrocytoma cell lines (LGG275, LGG336, LGG85, LGG349) derived from IDH-mutant astrocytomas of different grades and analyzed them using multi-omics approaches. These lines display growth rates in vitro and in vivo consistent with tumor grade and recapitulate some key molecular alterations observed in patient tumors, including IDH1, ATRX, and TP53 mutations, ALT (alternative lengthening of telomeres) activation and, in more aggressive lines, MET and PDGFRA alterations. Single-cell RNA sequencing revealed three major transcriptional states (astrocyte-like, oligodendrocyte-like, and NPC-like), consistent with those described in patient tumors. A hallmark of higher-grade-derived lines (LGG85, LGG349) is the persistence of NPC-like populations without growth factors possibly reflecting tumor progression. The LGG275 line most accurately mirrors slow-growing astrocytomas. Using CD44 and GLAST, we isolated astrocyte-like (CD44⁺/GLAST⁺) cells from LGG275 that preferentially adopt a quiescent state yet retain remarkable plasticity, generating oligodendrocyte-like cells (CD44⁻/GLAST⁻). Transcriptomic and proteomic analyses revealed that astrocyte-like and oligodendrocyte-like cells populations resemble, respectively, quiescent and activated neural stem (NSC) cells from the adult subventricular zone (SVZ). Finally, we provide evidence that NOTCH signaling contributes to the regulation of cell state balance, promoting transitions toward an astrocyte-like transcriptional program while DLL3, an anti-Notch protein, expressed by oligodendrocyte-like cells, modulates both proliferation and phenotype. These cell lines represent valuable resources for dissecting lineage dynamics, heterogeneity, and progression mechanisms in IDH-mutant astrocytomas.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534874","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":"Correction: NSC-derived extracellular vesicles-mediates neuronal plasticity enhancement in vascular dementia via transferring miR-210.","authors":"Qunwen Pan, Yan Wang, Zhi Xiang, Yulan Yin, Yuyan Deng, Kesheng Xiao, Xiaobing Xu, Yahong Wang, Ganwen Deng, Xiaoxia Wang, Wangtao Zhong, Xiaotang Ma","doi":"10.1186/s40478-026-02358-z","DOIUrl":"10.1186/s40478-026-02358-z","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"14 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497090","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}

{"title":"Multimodal molecular mapping of the vasculature in human cortex reveals lipid markers of cerebral amyloid angiopathy.","authors":"Cody R Marshall, Felipe A Moser, Claire F Scott, Lissa Ventura-Antunes, Wilber Romero-Fernandez, Łukasz G Migas, Léonore E M Tideman, Madeline E Colley, Martin Dufresne, Matthew S Schrag, Raf Van de Plas, Jeffrey M Spraggins","doi":"10.1186/s40478-026-02361-4","DOIUrl":"10.1186/s40478-026-02361-4","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy (CAA) commonly co-occurs with Alzheimer's disease (AD), yet the molecular changes that accompany vascular [Formula: see text]-amyloid deposition in human tissue remain incompletely defined. Herein, we use a novel imaging approach that combines matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS) with immunofluorescence microscopy on the same sections of postmortem human frontal cortex to map the lipid microenvironment of leptomeningeal vasculature in cases with and without CAA. Autofluorescence-guided regions-of-interest were imaged by IMS in both negative and positive ion modes and registered to post-IMS-acquired microscopy images. Immunofluorescence microscopy using markers for collagen IV, [Formula: see text]-smooth muscle actin ([Formula: see text]SMA), and thiazine red enabled automated segmentation of total, amyloid-positive, and amyloid-negative vasculature regions. A CAA index, the ratio of amyloid-positive area to total vasculature area in a region imaged by IMS, was used to define vasculature and classify each case into having CAA, or CAA-present, and not having CAA, or CAA-absent. An interpretable machine learning approach (XGBoost models with Shapley additive explanations for interpretation) was trained on pixel-level spectra and identified lipid signatures of vascular identity shared across groups as well as class-specific marker candidates that distinguished CAA-present from CAA-absent vasculature. CAA-absent vessels were characterized by higher contributions from phosphatidylserines (e.g., long-chain polyunsaturated PS species). Univariate differences were inconsistent between the two groups, but multivariate models in negative mode yielded stable discriminatory features. These results define spatial lipid correlates of vascular amyloid pathology in the human brain and establish a multimodal framework for mechanistically linking lipid metabolism, vascular integrity, and CAA in AD.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497006","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}

{"title":"Platelet transcriptomic signatures in pediatric brain tumors distinguish cancer from cancer-free control.","authors":"Markus Talka, Amanda Holmström, Jonathan Hiekka, Matti Kankainen, Satu Långström, Mia Westerholm-Ormio, Anu M Suominen, Ruth Nousiainen, Pirjo Isohanni, Pia Valle, Elina Välkesalmi, Oskar Saijonmaa, Atte Karppinen, Päivi Koroknay-Pal, Anna Piippo-Karjalainen, Jarno Satopää, Nuutti Vartiainen, Jukka Kanerva, Olli Tynninen, Soili Kytölä, Anna-Kaisa Anttonen, Virve Pentikäinen, Katja Eloranta","doi":"10.1186/s40478-026-02375-y","DOIUrl":"10.1186/s40478-026-02375-y","url":null,"abstract":"<p><p>Malignant pediatric brain tumors remain the leading cause of cancer-related mortality in children. Current diagnostics and monitoring rely on imaging and invasive biopsy, which may not capture tumor heterogeneity. Liquid biopsy-based biomarkers offer a novel, minimally invasive option. Among these, tumor-educated platelets have shown diagnostic value in adult cancers, but their utility in pediatric brain tumors has not been investigated. We analyzed platelet transcriptomes of 73 blood samples from 23 pediatric brain tumor patients, classified as high-grade or low-grade tumor patients, and 25 cancer-free controls. Platelets were isolated, CD45⁺ depleted, and subjected to RNA sequencing. CD45⁺ depletion efficiency was assessed using xCell-based leukocyte enrichment scores. Differential gene expression was assessed with DESeq2 and Gene Ontology over-representation analysis. Gene-level discrimination between groups was evaluated by receiver operating characteristic analysis, and a logistic regression model with patient-grouped 5-fold cross-validation was trained to classify high-grade tumor patients versus controls. Platelets from brain tumor patients showed transcriptional remodeling compared to controls, especially pronounced in high-grade tumor patients. We identified 315 and 338 differentially expressed genes in the brain tumor group versus controls and high-grade tumor patients versus control comparisons, respectively, and 9 genes in high-grade tumor patients versus low-grade tumor patients. In low-grade tumor patients versus controls, 30 genes met the significance threshold. Platelet gene expression of high-grade tumor patients showed consistent dysregulation of cancer-associated genes. Gene enrichment analyses highlighted pathways related to cytoskeleton dynamics, angiogenesis, and extracellular matrix organization. Multiple genes demonstrated encouraging classification performance, and logistic regression classifier based on selected transcripts achieved an area under the curve of 0.91, sensitivity of 85%, and a specificity of 92% in identifying high-grade tumor patients. This study provides the first evidence that platelets exhibit distinct transcriptomic signatures in pediatric brain tumor patients. Platelet RNA profiles separated high-grade tumor patients from controls, possibly reflecting tumor presence. These findings suggest that platelet transcriptomic profiling may warrant further investigation as a potential minimally invasive biomarker for pediatric brain tumors. The observed transcriptomic alterations and enriched pathways also raise the possibility that platelets participate in tumor-associated biological processes. Larger multicenter studies are needed to validate clinical applicability.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454238","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}

{"title":"Successful bioassay of blood from chronic wasting disease-affected cervids in cervid PrP transgenic Drosophila.","authors":"Alana M Thackray, Erin E McNulty, Amy V Nalls, Marcelo H Jorge, Michael J Chamberlain, Mark G Ruder, Candace K Mathiason, Raymond Bujdoso","doi":"10.1186/s40478-026-02372-1","DOIUrl":"10.1186/s40478-026-02372-1","url":null,"abstract":"<p><p>Chronic wasting disease is a fatal transmissible prion condition of free-ranging and farmed cervids including deer, elk, moose, muntjac and reindeer. Prionemia is a pathogenic feature of chronic wasting disease in cervids and underpins development of an ante-mortem blood test for effective disease management. To help achieve this goal, we show here that cervid PrP transgenic Drosophila can detect prion-infected blood from cervids with chronic wasting disease. We first established that cervid PrP Drosophila were highly sensitive to cervid prions since these flies were responsive to dilutions in the range of 10^- 2 to ≥ 10^- 10 of brain homogenate from terminal chronic wasting disease-affected cervids. We subsequently showed cervid PrP Drosophila developed a neurotoxic phenotype, evidenced by accelerated loss of locomotor activity and survival, after exposure to blood from cervids with experimental or natural chronic wasting disease. Cervid PrP Drosophila were sensitive to whole blood and blood fractions including plasma, buffy coat and different leukocyte subsets isolated from prion disease-affected cervids. Importantly, we showed that cervid PrP Drosophila were sensitive to blood samples isolated from chronic wasting disease-affected cervids during the pre-clinical phase of the condition. Significantly, we demonstrated that the neurotoxic fly phenotype which developed after exposure to prion-infected cervid blood was transmissible but was not associated with the accumulation of RT-QuIC-detectable prion seeding activity, which does occur after exposure to brain-derived cervid prions. Our data show that cervid PrP Drosophila can successfully detect blood from CWD-affected cervids and indicate that blood-borne prions have distinct propagation properties in PrP transgenic Drosophila compared to brain-derived prions.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454235","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}

{"title":"NOP56 is essential for mammalian generation and maintenance of multiple central nervous systems, associated with SCA36 pathology.","authors":"Kosuke Matsuzono, Yasumitsu Nagao, Chihiro Sarai, Yuki Takayanagi, Eiji Sakashita, Kazumasa Sekiguchi, Hiroyuki Honda, Akemi Makino, Kazuhiro Saito, Hitoshi Endo, Tatsushi Onaka, Shigeru Fujimoto","doi":"10.1186/s40478-026-02379-8","DOIUrl":"10.1186/s40478-026-02379-8","url":null,"abstract":"<p><p>NOP56, a core nucleolar component involved in small nucleolar ribonucleoprotein assembly, has been genetically implicated in spinocerebellar ataxia type 36. However, the role of NOP56 in mammalian neurodevelopment and disease remains poorly defined. We investigated NOP56 pathobiology using both in vitro induced pluripotent stem cell-derived neurons and in vivo NOP56 knockout mouse models. NOP56 expression significantly decreased both in the spinocerebellar ataxia type 36 patients induced pluripotent cells and induced pluripotent cell-derived neurons, which suggests the possibility that the NOP56 loss of function is involved in the spinocerebellar ataxia type 36 phenotype. Therefore, we generated and validated the NOP56 knockout mouse phenotype. Homozygous NOP56 deletion resulted in total embryonic lethality; no NOP56^-/- progeny was viable at birth. Heterozygous knockouts showed clasping at 8 months of age and had a larger body size with aging, although there was no significant difference in survival between heterozygous and wild type. Heterozygous knockout mice showed deterioration in rotarod performance and a decrease in exploration behavior. Immunohistochemical analysis of the heterozygous knockouts revealed widespread, significant central nervous system abnormalities, particularly cerebellar degeneration, accompanied by motor cortex and spinal cord disturbances. Widespread ubiquitin-positive inclusions were detected in the cerebellum, motor cortex, and anterior spinal cord of the heterozygous knockout mice at the 12-month age, and it was positive from the 6-month age in the cerebellum. Colocalizations of TDP-43 and ubiquitin were observed in the motor cortex, spinal cord, and cerebellum. Along with findings from previous reports showing early downregulation of NOP56 in SOD1 G93A transgenic mice, this finding indicates that NOP56 might be involved in a wide range of motor neuron diseases. The pathological characteristics of the NOP56 heterozygous knockouts are like those of a patient with spinocerebellar ataxia type 36. Results reveal that NOP56 is indispensable for mammalian embryogenesis and central nervous system maintenance, and that its reduction contributes to molecular pathology in spinocerebellar ataxia type 36. These findings uncover a convergent neurodegenerative mechanism and identify NOP56 as a potential therapeutic target.Clinical trial registrationThis study was registered with the Japan Clinical Trials Registry (http//umin.ac.jp/ctr/index/htm), under the number UMIN000047097.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429579","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}

{"title":"Repeated mild spinal cord contusions exacerbate tauopathy development in PS19 mice.","authors":"Nicolas Halloin, Nicolas Debortoli, Lidia Lopez-Gutiérrez, Hélène Collignon, Zoé Marlier, Kunie Ando, Valérie Suain, Louise Conrard, Margaux Mignolet, Lindsay Sprimont, Marino Caruso, Aurélie Ladang, Jonathan Degosserie, Karelle Leroy, Charles Nicaise","doi":"10.1186/s40478-026-02378-9","DOIUrl":"10.1186/s40478-026-02378-9","url":null,"abstract":"<p><p>Growing evidence indicates that traumatic brain injury constitutes a significant risk factor for the development of age-related tauopathies, yet the consequences of repeated mild spinal cord injuries (rmSCI) remain insufficiently explored. In this context, we developed a mouse model undergoing two successive mild cervical contusions during young adulthood, which do not produce immediate functional motor deficits, thereby mimicking real-life conditions of occupational- or sports-related trauma. rmSCI were induced in PS19 (hTau^P301S) mice developing late-onset tauopathy in the brain and in the spinal cord. The consequences of rmSCI were assessed on motor outcomes and tauopathy signature in injured PS19 mice during ageing. rmSCI exacerbated age-dependent motor deficits and significantly increased tau hyperphosphorylation on the pSer422 and pSer202/Thr205 epitopes. Pathological changes, initially confined to the epicenter of the contusions, extended along a caudo-rostral axis reaching the thalamus. While rmSCI did not modify intraspinal tau aggregation, spinal cord-derived protein extracts displayed enhanced seeding activity in vitro. Although causality was not established with tau hyperphosphorylation status, early response towards mild spinal contusions included p38 MAPK activation, glial activation and upregulation of interferon-stimulated genes. Together, these data identify rmSCI as a previously underappreciated modifier of tau pathology and disease progression. Moreover, this study provides a novel experimental link between mild central nervous system injuries and exacerbation of tauopathy and suggests the involvement of type I interferon signalling or sustained glial activation. Ultimately, these findings underscore the importance of preventing even mild spinal injuries in individuals at risk of tauopathy.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417701","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}

{"title":"Context of use matters: interpreting extracellular vesicle TDP-43 as a biomarker in ALS.","authors":"Jenna M Gregory","doi":"10.1186/s40478-026-02376-x","DOIUrl":"10.1186/s40478-026-02376-x","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417674","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}