Acta Neuropathologica最新文献

{"title":"Risk stratification for meningiomas with discordant molecular classification","authors":"Brooke C. Braman, Ayush Aggarwal, Minh P. Nguyen, Kanish Mirchia, William C. Chen, David R. Raleigh","doi":"10.1007/s00401-026-03038-x","DOIUrl":"10.1007/s00401-026-03038-x","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305062","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":"Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP","authors":"Przemysław R. Kac,&nbsp;Katheryn A. Q. Cousins,&nbsp;Alicja Szadziewska,&nbsp;Leslie M. Shaw,&nbsp;Michael Turton,&nbsp;Vivianna M. Van Deerlin,&nbsp;Peter Harrison,&nbsp;Henrik Zetterberg,&nbsp;David A. Wolk,&nbsp;Corey T. McMillan,&nbsp;Douglas Galasko,&nbsp;Jörg Hanrieder,&nbsp;Edward B. Lee,&nbsp;Hlin Kvartsberg,&nbsp;David J. Irwin,&nbsp;Kaj Blennow","doi":"10.1007/s00401-026-03042-1","DOIUrl":"10.1007/s00401-026-03042-1","url":null,"abstract":"<div><p>Across tauopathies—Alzheimer’s disease (AD), frontotemporal lobar degeneration due to tau (FTLD-tau)—we compared cerebrospinal fluid (CSF) biomarkers of phosphorylated-tau (p-tau) p-tau181, p-tau212, tau368, total tau (t-tau), and the tau368/t-tau ratio, and tested differentiation from non-tau (FTLD-TDP, neuronal α-synuclein disease (αSyn), and controls). In AD, CSF p-tau181 and p-tau212 were significantly higher than in all other groups, including FTLD-tau, while tau368/t-tau was significantly lower. With the aim to combine tau phosphorylation biomarkers (p-tau181 and p-tau212) with biomarkers for severity of tau pathology (tau368), we made ratios between these biomarkers and examined their diagnostic accuracy in FTLD after excluding high/intermediate AD neuropathologic change (ADNC). CSF p-tau181 and p-tau212, as well as p-tau181/tau368 and p-tau212/tau368, were higher in FTLD-tau compared with non-tau groups, and the diagnostic accuracy to discriminate FTLD-tau from FTLD-TDP improved. Levels of the ratios were increased in behavioral and primary progressive aphasia variants of tauopathies when compared to FTLD-TDP. Furthermore, the biomarkers showed significant correlation with both FTLD-tau and AD tau burden at autopsy across brain regions. These results suggest unique patterns of increased relative levels of p-tau epitopes in CSF among ADNC and FTLD-tau could improve the diagnosis of tauopathies and inform inclusion criteria in clinical trial design.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03042-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305065","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":"CTE has multiple pathologic variants that might relate to different clinical symptom presentation","authors":"Fatima Tuz-Zahra,&nbsp;Eli Hallowell,&nbsp;Chris Tilton,&nbsp;Victor E. Alvarez,&nbsp;Nurgul Aytan,&nbsp;Samantha Hawkins,&nbsp;Jesse Mez,&nbsp;Michael Alosco,&nbsp;Ann C. McKee,&nbsp;Yorghos Tripodis,&nbsp;Thor D. Stein,&nbsp;Jonathan D. Cherry","doi":"10.1007/s00401-026-03045-y","DOIUrl":"10.1007/s00401-026-03045-y","url":null,"abstract":"<div><p>Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease found in individuals with a history of repetitive head injury (RHI) received through playing contact sports. Currently, CTE can only be diagnosed after death through the identification of perivascular neuronal hyperphosphorylated tau (pTau) pathology, found at the depth of the cortical sulcus. Although the pathognomonic lesion is found among all cases, pTau deposition is patchy and heterogeneous among individuals. To determine whether the heterogeneity of CTE masks more subtle ordering or additional disease variants, we applied the unsupervised machine learning algorithm subtype and stage inference (SuStaIn) on fully quantitative pTau density data from 26 brain regions in 207 CTE cases and 75 control cases. SuStaIn identified three distinct pathological progression subtypes: 93 cases were classified as Subtype 1 (cortical predominant) and showed dense, rapidly progressing cortical pTau akin to the classically described CTE neuropathology; Subtype 2 (cortical sparing–hippocampal enhanced) had 105 cases that exhibited a reduced cortical pTau burden that progressed slower, but also had pronounced hippocampal involvement in a CTE-specific pattern; and Subtype 3 (copathology altered) consisted of 28 older cases with higher CTE stage, was enriched for comorbid pathologies (pTDP43, Aβ, hippocampal sclerosis, and arteriolosclerosis), and had enhanced pTau in regions highly related to those additional pathologies. Clinically, impaired performance in the Functional Activities Questionnaire (FAQ) correlated with pTau regional burden and severity only in cases with Subtype 1 pathology, suggesting the enhanced cortical pTau pathology was linked to greater functional decline. Overall, these findings help characterize the heterogeneity in CTE progression, validate key pathological variants, and will be crucial for refining diagnostic criteria and advancing in-life diagnosis.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03045-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299056","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":"Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer’s disease","authors":"Lindsay A. Welikovitch,&nbsp;Derek H. Oakley,&nbsp;Rachel E. Bennett,&nbsp;Alberto Serrano-Pozo,&nbsp;Haoyang Zhu,&nbsp;Nancy E. Ruiz-Uribe,&nbsp;Theodore J. Zwang,&nbsp;Lori B. Chibnik,&nbsp;Teresa Gomez-Isla,&nbsp;Matthew P. Frosch,&nbsp;Donald S. Marks,&nbsp;Stephen Salloway,&nbsp;Charles Bernick,&nbsp;David Greeley,&nbsp;Caitlin S. Latimer,&nbsp;Amber Nolan,&nbsp;R. Matthew Hutchison,&nbsp;Carrie E. Rubel,&nbsp;Thierry Bussiere,&nbsp;Edward D. Plowey,&nbsp;C. Dirk Keene,&nbsp;Bradley T. Hyman","doi":"10.1007/s00401-026-03037-y","DOIUrl":"10.1007/s00401-026-03037-y","url":null,"abstract":"<div><p>Fluid and imaging biomarker data show that anti-amyloid (Aβ) antibodies promote the clearance of Aβ from the brains of patients with Alzheimer’s disease (AD). We examined <i>postmortem</i> brain tissue of individuals who participated in aducanumab clinical trials and investigated the drug’s effects on Aβ pathology and other AD phenotypes. The medial temporal lobe of six aducanumab clinical trial participants—who had extensive exposure to aducanumab and happened to die between 7 weeks and 5 years after their last antibody infusion—was compared with that of nine untreated AD patients matched for age, <i>APOE</i> genotype, and Braak neurofibrillary tangle stage, to determine how aducanumab impacts AD pathobiology. Patients treated with aducanumab displayed a robust reduction in Aβ burden. As observed in previous studies, Aβ was associated with non-arterial microvessels in aducanumab-treated patients, suggesting a redistribution of Aβ within the neuropil. Neuritic phospho-tau decreased in parallel with fewer Aβ plaques, but the density of PHF-1⁺ and AT8⁺ neurofibrillary tangles remained unchanged relative to the average untreated AD donor. Measures of microglial and astroglial reactivity were also comparable to those in untreated AD controls. These findings confirm aducanumab’s potent ability to target and remove brain Aβ. On average, Aβ plaques increased in proportion to the length of time after the last dose, consistent with the idea that plaques gradually redeposit post-treatment. The selective reduction of neuritic, but not neurofibrillary tangle phospho-tau implies that Aβ-targeted antibodies such as aducanumab alleviate plaque-associated dystrophy but may not address established tangles. This study describes the long-term outcomes of anti-Aβ immunotherapy in AD.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03037-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256913","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":"Expression of GPR34 in microglia remains stable in human Alzheimer’s disease","authors":"Sophie Seiffer,&nbsp;Jonas Rotter,&nbsp;Jana Brendler,&nbsp;Albert Ricken,&nbsp;Zoe Detzer,&nbsp;Max Braune,&nbsp;Torsten Schöneberg,&nbsp;Angela Schulz,&nbsp;Karsten Winter,&nbsp;Ingo Bechmann","doi":"10.1007/s00401-026-03035-0","DOIUrl":"10.1007/s00401-026-03035-0","url":null,"abstract":"<div><p>Microglia are the resident immune cells of the human central nervous system and play key roles in development, homeostasis, and disease. These functions are mediated by a broad repertoire of cell-surface receptors, including G protein-coupled receptors such as the ADP receptor P2Y12 and GPR34, a receptor for lysophosphatidylserine. While GPR34 deficiency has been linked to impaired microglial phagocytosis, its regulation in relation to amyloid-β (Aβ) and tau pathology in Alzheimer’s disease (AD) remains unclear. We performed a quantitative analysis of microglial density, morphology, and GPR34 expression in the medial temporal lobe cortex (MTLC) of elderly human body and tissue donors across the AD spectrum. Using fluorescence in situ hybridization and immunolabeling, we analyzed 187,670 microglial cells and correlated microglial parameters with the severity and spatial proximity of Aβ plaques and tau inclusions. In parallel, we analyzed human single-nucleus RNA sequencing data from 236,002 cells to assess GPR34 expression across microglial subtypes, brain regions, and neuropathological stages. Microglial density and overall morphology in the MTLC were largely preserved, independent of local Aβ or hyperphosphorylated tau burdens. Apart from a moderate shortening of microglial processes in the immediate vicinity of Aβ plaques, no consistent pathology-associated morphological changes were detected. GPR34 expression showed pronounced cell-to-cell variability and differed across microglial subtypes and brain regions, but neither expression intensity nor the proportion of GPR34-positive microglia correlated consistently with Braak stage or Thal phase. These findings suggest that GPR34 regulation in human microglia is highly context-dependent and shaped by regional and cellular heterogeneity rather than AD-associated pathology alone.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03035-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248756","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":"Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants","authors":"Nurun N. Fancy,&nbsp;Nanet Willumsen,&nbsp;Vicky M. N. Chau,&nbsp;Samuel L. Boulger,&nbsp;Harry J. Whitwell,&nbsp;Wenhao Wang,&nbsp;Baptiste Avot,&nbsp;Michael Thomas,&nbsp;Jonathan Talbot-Martin,&nbsp;Stergios Tsartsalis,&nbsp;Combiz Khozoie,&nbsp;Aisling McGarry,&nbsp;Eleonore Schneegans,&nbsp;Riad Yagoubi,&nbsp;To Ka Dorcas Cheung,&nbsp;Marianna Papageorgopoulou,&nbsp;Emily Adair,&nbsp;Benjamin Cooper,&nbsp;Karen Davey,&nbsp;Amy M. Smith,&nbsp;William Scotton,&nbsp;John Hardy,&nbsp;Paul M. Matthews,&nbsp;Johanna S. Jackson","doi":"10.1007/s00401-026-03036-z","DOIUrl":"10.1007/s00401-026-03036-z","url":null,"abstract":"<div><p><i>TREM2</i> plays multiple functional roles in microglia and variants are associated with increased risks of Alzheimer’s disease (AD). Genetic polymorphisms reducing expression of the functionally related protein CD33 are protective. Here we have contrasted cellular pathology in human post-mortem brain with and without AD to test mechanisms associated with the differential genetic risks conferred by <i>R47H</i> and <i>R62H TREM2</i> variants (<i>TREM2var</i>) with and without heterozygosity for the protective rs3865444 <i>CD33</i> polymorphism. Epistasis between <i>CD33</i> and <i>TREM2</i> was demonstrated by relative normalisation of differences in β-amyloid load in <i>TREM2var</i> carriers of the protective <i>CD33</i> allele. These functional differences were mirrored by differential microglial transcriptomic responses to β-amyloid. Controlling for <i>CD33</i> genotype, microglial transcriptional responses to increasing β-amyloid were lower for <i>TREM2var</i>, particularly for <i>R47H</i> compared to <i>CV</i>, and there was a reduction in expression of neuroplasticity pathways in <i>TREM2var. R62H</i> microglial signatures were distinguished from those of <i>R47H</i> by upregulation of genes associated with phagocytosis and from <i>CV</i> by differences in inflammatory gene expression including those involved in NF-kappaB signalling. Differential gene expression with increasing β-amyloid also suggested upregulation of β-amyloid production and binding pathways in excitatory neurons in <i>TREM2var</i> heterozygotes. There was lower enrichment for pathways positively adaptive to pathology and expressed in inhibitory neurons from <i>CV</i> samples for both <i>TREM2var.</i> Exploratory bulk tissue proteomics support these observations with evidence for adaptive plasticity in response to β-amyloid pathology in <i>CV</i> tissue not found for the <i>TREM2var,</i> which showed evidence of increased β-amyloid formation and neuroplasticity changes. Together, these results highlight differences in molecular pathology between <i>CV</i> and <i>TREM2var</i> and between the <i>TREM2var</i> risk variants. They highlight mechanisms of AD risk mediated by secondary effects on astroglial and neuronal functions. Demonstration of strong epistasis between <i>TREM2</i> and <i>CD33</i> with AD supports the therapeutic potential of modulators of <i>CD33</i> inhibition or expression.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03036-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256905","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":"AETA peptide contributes to Alzheimer’s disease signature of synapse dysfunction","authors":"Jade Dunot,&nbsp;Carine Gandin,&nbsp;Marin Truchi,&nbsp;Giulia Pirro,&nbsp;Sébastien Moreno,&nbsp;Agathe Launay,&nbsp;Benjamin Azoulay,&nbsp;Hugo Landra,&nbsp;Sandy Ma Yishan,&nbsp;Luc Buée,&nbsp;Kevin Lebrigand,&nbsp;Paula A. Pousinha,&nbsp;David Blum,&nbsp;Bernard Mari,&nbsp;Ingrid Bethus,&nbsp;Michael Willem,&nbsp;Hélène Marie","doi":"10.1007/s00401-026-03033-2","DOIUrl":"10.1007/s00401-026-03033-2","url":null,"abstract":"<div><p>Alzheimer’s disease (AD), the leading cause of dementia, is characterized by early synaptic dysfunction that precedes overt cognitive decline. While amyloid-β and Tau remain central to AD pathogenesis, molecular triggers of synapse weakening remain unclear. Here, we investigated AETA, a novel brain-secreted peptide derived from amyloid precursor protein (APP), as a potential mediator of synapse dysfunction in AD. We previously identified AETA as a unique modulator of NMDA receptor activity in the healthy brain; however, its role in AD etiology was yet to be explored. Post-mortem analyses of human hippocampal and prefrontal cortex tissues revealed significantly elevated AETA levels in AD patients, particularly in females. To further explore the contribution of AETA to AD synaptic pathology, we analyzed a new mouse model, the AETA-m mouse, exhibiting chronically increased brain AETA expression. Hippocampi of female AETA-m mice displayed an increase in the number of astrocyte and microglia, but no overt neuroinflammation. RNA sequencing of female AETA-m hippocampi revealed alterations in synaptic gene expression that closely paralleled those observed in vulnerable human AD brain regions, most notably in the hippocampus. These two phenotypes were absent in males. Functionally, hippocampal neurons from AETA-m mice displayed impaired NMDA receptor signaling, dendritic spine loss, and memory deficits especially in females, mirroring early AD-associated synaptic dysfunction. Together, these findings identify AETA as a novel key contributor of synaptic vulnerability in AD and associated memory processing, especially in females. Targeting AETA signaling may therefore offer new therapeutic avenues for preventing or mitigating synaptic and cognitive decline in AD.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-026-03033-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154808","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":"GRP78 associates with alpha-synuclein in vulnerable neurons of the Parkinson’s disease brain","authors":"Dominik Hrabos,&nbsp;Anna Mrowiecova,&nbsp;Jitka Cicmancova,&nbsp;Jiri Ehrmann","doi":"10.1007/s00401-026-03034-1","DOIUrl":"10.1007/s00401-026-03034-1","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100842","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":"Reevaluating the role of beta2-microglobulin: new insights on selective vulnerability in ALS pathology","authors":"Melanie Leboeuf,&nbsp;Jik Nijssen,&nbsp;Laura Helen Comley,&nbsp;Julio Cesar Aguila Benitez,&nbsp;Irene Mei,&nbsp;Silvia Gómez Alcalde,&nbsp;Ramón A. Muñoz de Bustillo-Alfaro,&nbsp;Vlad Radoi,&nbsp;Susanne Nichterwitz,&nbsp;Christoph Schweingruber,&nbsp;Abraham Acevedo Arozena,&nbsp;Eva Hedlund,&nbsp;Staffan Cullheim","doi":"10.1007/s00401-026-03024-3","DOIUrl":"10.1007/s00401-026-03024-3","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) is characterized by the selective loss of motor neurons (MNs). Why these neurons are particularly vulnerable in ALS remains unclear, as does why certain MN groups remain resistant throughout the disease course. We investigated the role of the human leukocyte antigens (HLAs) and beta2-microglobulin (β2m) in MN susceptibility to ALS, given their reported involvement in both prolonging and shortening disease progression. Loss of HLAs in ALS has also been shown to increase MNs vulnerability to toxicity exerted by activated astrocytes. RNA sequencing of control tissues demonstrated that disease-resistant oculomotor neurons (OMNs) and Onuf’s MNs exhibited <i>β2m</i> and <i>HLA</i> mRNA levels comparable to those of vulnerable spinal MNs, suggesting that baseline differences in these transcripts do not explain the differential vulnerabilities of these MN groups. However, HLA protein levels showed an inverse correlation with spinal MN size, with the large MNs, those lost early in ALS, displaying the lowest HLA expression. HLA protein levels were also reduced in spinal MNs from end-stage ALS patient tissues, while remaining relatively unchanged in OMNs. In contrast, spinal MNs uniquely exhibited significant upregulation of <i>β2m</i> and <i>HLA-C</i> transcripts during disease, likely reflecting a protective compensatory response. Together, these findings suggest that β2m and HLAs may contribute to spinal MN vulnerability in ALS. To assess their functional role, β2m knockout mice were crossbred with SOD1G93A ALS mice. Loss of β2m did not alter life span of the ALS mice, but led to partial preservation of lumbrical muscle innervation that was insufficient to maintain motor function. Analysis of GFAP immunoreactivity revealed marked neuroinflammation activation in the spinal cords of β2m knockout mice. As these mice retain normal MN numbers and life-span, this indicates that loss of functional MHC-I, even in the presence of astrocyte activation, is insufficient to cause MN disease. Furthermore, β2m knockout significantly increased GFAP activation in SOD1G93A mice, but did not further exacerbate disease progression, suggesting that loss of functional MHC-I does not necessarily render MNs more vulnerable to astrocyte toxicity. Overall, these findings indicate that β2m and HLAs are dynamically regulated in ALS, and may influence MN vulnerability, but they are not major disease modifiers in ALS.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051843","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":"TANC1::HTRA1 and KPNA4::WWTR1 fusions in non-vestibular intracranial schwannomas","authors":"Takahiro Tsuchiya,&nbsp;Satoru Miyawaki,&nbsp;Yudai Hirano,&nbsp;Yu Sakai,&nbsp;Kenta Ohara,&nbsp;Yohei Inoue,&nbsp;Daisuke Komura,&nbsp;Aya Shinozaki-Ushiku,&nbsp;Shotaro Ogawa,&nbsp;Daisuke Sato,&nbsp;Hiroki Hongo,&nbsp;So Hirata,&nbsp;Yu Teranishi,&nbsp;Hideaki Ono,&nbsp;Yoshihiro Otani,&nbsp;Hirokazu Takami,&nbsp;Tetsuo Ushiku,&nbsp;Shumpei Ishikawa,&nbsp;Shota Tanaka,&nbsp;Koichi Ichimura,&nbsp;Nobuhito Saito","doi":"10.1007/s00401-026-03032-3","DOIUrl":"10.1007/s00401-026-03032-3","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"151 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025630","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}