Brain Pathology最新文献

{"title":"Effects of postmortem interval on myelin integrity in rhesus macaque brain tissue.","authors":"Anna Novoseltseva, Rhiannon Robinson, Peter Niziolek, Allen Jang, Ting Xie, Ankita Tiwari, Ayman Abdelhakeem, Raymond Nicks, Yvonne Lucas, Qiong Yang, Farzad Mortazavi, David Boas, Hui Wang, Tara L Moore, Douglas L Rosene, Irving J Bigio","doi":"10.1111/bpa.70158","DOIUrl":"10.1111/bpa.70158","url":null,"abstract":"<p><p>When conducting microscopy of human brain sections, the postmortem interval (PMI) introduces myelin-related artifacts that can confound neuropathological interpretation, yet the extent and detectability of these changes remain poorly characterized. This study examined the impact of controlled PMI on myelin integrity in rhesus macaque brain tissue using advanced optical imaging approaches. Brains from five aged rhesus macaques (20.5-28.5 years) were maintained at 4°C and analyzed at 0, 24, and 72 h postmortem. Myelin integrity in white and gray matter was assessed using quantitative birefringence microscopy to measure relative retardance and polarization-sensitive optical coherence tomography to quantify scattering coefficients, retardance, and volumetric features. Increasing PMI was associated with progressive myelin degradation, reflected by significant reductions in relative optical retardance in white matter (p < 0.01) and gray matter (p < 0.001), alongside increased scattering coefficients in both regions (p < 0.001). Morphological analyses revealed a marked increase in myelin defects per mm² with longer PMI (p < 0.001), characterized by swellings, vesicles, and structural discontinuities. These findings demonstrate that PMI causes significant detectable myelin changes, which can be quantified using optical imaging techniques, providing critical implications for interpreting postmortem neuropathological studies (especially with human brain tissues) and establishing a need for standardized PMI considerations in research protocols to ensure accurate pathological assessment in neurological disease investigations.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70158"},"PeriodicalIF":5.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206590","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":"Chronic traumatic encephalopathy in a neuropathologically confirmed Creutzfeldt-Jakob disease cohort.","authors":"Lluc Bertran, Iban Aldecoa, Arlène Sindikubwabo, Núria Vidal, Rafael Blesa, Mercè Martínez-Corral, Carlos Nos, Verónica Santiago, Andrea González, Álex Iranzo, Christopher J Nowinski, Ann C McKee, Raquel Sánchez Valle, Laura Molina-Porcel","doi":"10.1111/bpa.70156","DOIUrl":"10.1111/bpa.70156","url":null,"abstract":"<p><p>Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive head impacts, experienced most commonly in contact sports; however, its relationship with prion diseases remains unclear. Postmortem CTE screening using phosphorylated tau staining was conducted at the Neurological Tissue Bank of Hospital Clínic-IDIBAPS on hippocampal and frontal cortex samples from patients with neuropathologically confirmed Creutzfeldt-Jakob disease (CJD), blinded to patients' clinical histories. In positive and suggestive cases, the analysis was expanded in accordance with the NINDS/NIBIB consensus criteria for CTE, and clinical and neuropathological information was reviewed. CTE was detected in 3 out of 212 CJD cases (1.4%), all with severe CTE pathology: 2 former soccer players (one of them an elite player) and 1 former rugby player. All had started playing sports between the first and second decades of life and ended in the fifth. The clinical presentation of CJD was heterogeneous, with different initial symptoms in each case. Neuropathological examination revealed an MM1/MV1 histotype in the soccer players and a VV2 histotype in the rugby player, the first- and second-most common variants in CJD, respectively. These three cases illustrate the coexistence of CTE and CJD across heterogeneous clinicopathological presentations. Further studies are needed to determine whether shared mechanisms may contribute to the coexistence of both pathologies.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70156"},"PeriodicalIF":5.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179237","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":"Identifying regulatory muscle processes in infantile and adult Pompe patients using a multi-omic and morphological approach.","authors":"Alexander Schaiter, Keerthika Lohanadan, Alexander Mensch, Andreas Hentschel, Angela Rosenbohm, Cornelia Kornblum, Angela Roth, Tara Procida-Kowalski, Heidrun H Krämer, Andreas Hahn, Jörg Höhfeld, Dieter O Fürst, Werner Stenzel, Peter F M van der Ven, Andreas Roos, Marek Bartkuhn, Anne Schänzer","doi":"10.1111/bpa.70155","DOIUrl":"10.1111/bpa.70155","url":null,"abstract":"<p><p>Pompe disease is a lysosomal glycogen storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). There are two different clinical phenotypes, which are based on the age of onset, GAA variants, and residual enzyme activity. To better understand the regulation of age-dependent pathways in Pompe disease, we performed a multi-modal approach. We included mass spectrometry (MS) (liquid chromatography coupled to tandem mass spectrometry) and bulk-RNA sequencing on skeletal muscle samples from patients with late onset Pompe disease (LOPD) (n = 21) and infantile-onset Pompe disease (IOPD) (n = 11) naive to enzyme replacement therapy (ERT), IOPD patients with ERT (n = 5) and age-matched controls. The findings were verified by immunofluorescence studies and ultrastructural analysis using samples with different disease progression. We identified deregulated muscle processes in LOPD and IOPD samples, with different levels of regulation evident at the transcriptome and protein levels. Transcriptomic profiling revealed upregulation of immune processes in both Pompe subtypes, while metabolic processes were downregulated mainly in LOPD. Downregulation of transcripts associated with muscle development and myogenesis was only observed in IOPD samples. MS analysis revealed a decrease in the expression of sarcomeric proteins mainly in LOPD, while chaperone-assisted selective autophagy was altered in both Pompe subtypes. Proteins linked to vesicle trafficking and biosynthesis correlated with the degree of muscle pathology in LOPD, highlighting their role in the progression of the disease. IOPD patients treated with ERT showed normalised deregulated transcripts, though not fully back to baseline. Proteins increased with ERT were linked with mitochondrial and protein control pathways, and sarcomeric function, indicating ERT's positive effect on skeletal muscle function at the molecular level. Our findings reveal that combining a multi-omic approach, including morphological observations, enables the detection of a greater number of deregulated muscle processes, indicating both similar and distinct muscle processes in IOPD and LOPD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70155"},"PeriodicalIF":5.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126622","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":"Wasteosomes accumulate in periventricular white matter hyperintensities and exhibit complex relationships with mixed pathology, sclerotic index, and perivascular space","authors":"Nikita Ollen-Bittle,&nbsp;Isabella Boesgaard,&nbsp;Austyn Roseborough,&nbsp;Meaghan Frank,&nbsp;Qi Zhang,&nbsp;Stephen H. Pasternak,&nbsp;Robert Hammond,&nbsp;Shawn N. Whitehead","doi":"10.1111/bpa.70110","DOIUrl":"10.1111/bpa.70110","url":null,"abstract":"<p>Corpora amylacea or “wasteosomes” are discontinuous lipid labyrinth structures that are polyglucosan rich, retain cellular waste and are thought to be of astrocytic origin. Wasteosomes localize around periventricular (PV) regions, perivascular spaces (PVS), and sub-pial regions; and their accumulation has been found to correlate with aging, vascular disorders, neurodegenerative diseases, and conditions that impair sleep. White matter hyperintensities (WMHs) are diffuse hyperintense areas seen on T2-weighted or fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans that represent damage to white matter. PV WMHs are known predictors of mild cognitive impairment, stroke, dementia and death. The relationship between wasteosome accumulation, PV WMHs, vascular pathology and PVS is currently unknown. For the first time, in a mixed diagnostic cohort of pathologically diagnosed: Alzheimer's disease (AD), cerebrovascular disease (CVD), mixed AD/CVD, and control tissue with no pathological diagnosis, we connected the histopathological wasteosome profile in periventricular brain sections in relation to 7T FLAIR-MRI confirmed PV WMHs, vascular sclerosis and PVS. Our results reveal wasteosomes accumulate in PV WMHs, are increased in proximity to large PV venules, and exhibit complex relationships with WMH severity, mixed pathology, sclerotic index and PVS. These findings provide novel insights into the pathophysiology underlying white matter injury.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970423","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":"Dysregulated TIE-2 expression is associated with blood-brain barrier leakiness and Alzheimer's disease-related neuropathology","authors":"Selvi Ince,&nbsp;Carol Van Hulle,&nbsp;Gwendlyn Kollmorgen,&nbsp;Clara Quijano-Rubio,&nbsp;Carey Gleason,&nbsp;Barbara B. Bendlin,&nbsp;Ozioma Okonkwo,&nbsp;Sanjay Asthana,&nbsp;Kaj Blennow,&nbsp;Henrik Zetterberg,&nbsp;Sterling C. Johnson,&nbsp;Seth Love,&nbsp;J. Scott Miners","doi":"10.1111/bpa.70109","DOIUrl":"10.1111/bpa.70109","url":null,"abstract":"<p>Cerebral hypoperfusion and blood–brain barrier (BBB) leakiness are related to cognitive decline and the onset and spread of Aβ and tau pathology in Alzheimer's disease (AD). Disrupted angiopoietin/TIE (ANGPT/TIE) signalling causes neurovascular instability and BBB leakiness accelerating cognitive decline and disease pathology in mouse models of AD. To explore ANGPT/TIE signalling in human AD, we measured CSF TIE-1 and TIE-2 levels by ELISA in two independent clinical dementia cohorts, and serum and CSF Tie-1/-2 in paired CSF and serum samples from neurologically normal individuals. ANGPT1, ANGPT2, TIE-1 and TIE-2 levels were measured by ELISA in crude homogenate (CH) and microvessel-enriched fractions (MVFs) of post-mortem human parietal cortex in relation to biochemical markers of cerebral perfusion (MAG:PLP1) and BBB leakiness (parenchymal fibrinogen) in a control, AD, and vascular dementia (VaD) cohort. CSF soluble TIE-2 was elevated in AD biomarker+ve individuals and correlated positively with CSF t-tau and p-tau, and markers of BBB leakiness, neuronal injury, and neuroinflammation. Tissue TIE-2 levels were significantly reduced in Braak tangle stage (BS) III-IV, that is, brains with early-intermediate AD pathology, and were lower in MVFs in end-stage AD pathology (BSV-VI) than in controls or VaD. Lower levels of MVF TIE-2 correlated with markers of cerebral hypoperfusion and BBB leakiness. Our study reveals a reciprocal relationship between elevated CSF and reduced tissue TIE-2 expression that is related to markers of tau pathology, BBB leakiness, and cerebral hypoperfusion, providing novel insights into ANGPT/TIE signalling in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197368","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":"AOSNP-ADAPTR resource level-based recommendations on practical diagnostic strategies for ependymomas","authors":"Laveniya Satgunaseelan,&nbsp;Michael E. Buckland,&nbsp;Geeta Chacko,&nbsp;Kenta Masui,&nbsp;Junji Shibahara,&nbsp;Vani Santosh,&nbsp;Maysa Al-Hussaini,&nbsp;Sung-Hye Park,&nbsp;Tarik Tihan,&nbsp;Ho-Keung Ng,&nbsp;Pieter Wesseling,&nbsp;David N. Louis,&nbsp;Chitra Sarkar,&nbsp;Takashi Komori","doi":"10.1111/bpa.70114","DOIUrl":"10.1111/bpa.70114","url":null,"abstract":"<p>Ependymomas are uncommon primary tumors of the central nervous system (CNS) that affect both children and adults. In recent years, molecular analyses have identified multiple subtypes of ependymal tumors based on location, patterns of CpG island methylation, and gene fusion events. While this knowledge is highly important in progressing diagnostic precision, prognostication, and effective treatments, an unwanted side effect is that best practice diagnostics are often inaccessible because of cost and technical barriers for many low- or lower middle-income countries. The ADAPTR group (Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions) is an initiative of the Asian Oceanian Society of Neuropathology and aims to provide practical guidelines for CNS tumor diagnostics at various levels of pathology resource restrictions. In this manuscript, we propose a practical approach to the diagnosis of ependymal tumors based on ADAPTR resource levels. These recommendations provide a practical adaptation of World Health Organisation Classification of Tumours of the Central Nervous System guidelines suited to routine diagnosis in resource-restrained regions.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210002","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":"Society News","authors":"Audrey Rousseau","doi":"10.1111/bpa.70149","DOIUrl":"https://doi.org/10.1111/bpa.70149","url":null,"abstract":"&lt;p&gt;&lt;b&gt;&lt;i&gt;Future International Congresses of Neuropathology (ICNs) ICN27 Edinburgh&lt;/i&gt;&lt;/b&gt;. The International Congress of Neuropathology (ICN) will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).&lt;/p&gt;&lt;p&gt;“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.&lt;/p&gt;&lt;p&gt;Colin Smith&lt;/p&gt;&lt;p&gt;Congress President ISN 2027”&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;ICN31 Bangalore / Bengaluru&lt;/i&gt;&lt;/b&gt;. ISN is pleased to announce that the International Congress of Neuropathology 2031 (ICN31) will be hosted in Bangalore/Bengaluru, India, following a successful bid from the Neuropathology Society of India (NPSI). The congress is planned for the beginning of October 2031 (final dates to be confirmed). It will be the first time for the International Congress of Neuropathology to take place in India and we very much look forward to it. Congratulations to NPSI for preparing to host the first International Congress of Neuropathology in India. We will be receiving regular updates on congress planning and preparations including more formal updates at our Joint ISN Council &amp; Executive meetings in the coming years.&lt;/p&gt;&lt;p&gt;Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Brain Pathology has joined Wiley's Open Access&lt;/i&gt;&lt;/b&gt; portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich&lt;/i&gt;&lt;/b&gt;. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested colleagues are invited to use this resource, which will be particularly useful for teaching and training (see link below). Colleagues are invited to con","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099600","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":"Decoding neuronal vulnerability: Multidimensional analysis of D1R- and D2R- medium-sized spiny neurons in Huntington's disease","authors":"Guendalina Bergonzoni,&nbsp;Miguel Pellegrini,&nbsp;Aurora Savino,&nbsp;Martina Lazioli,&nbsp;Sarah Geurs,&nbsp;Lorenzo Graziani,&nbsp;Denise Ferrarini,&nbsp;Solaleh Khoramian Tusi,&nbsp;Esaria Oliver,&nbsp;Jarne Geurts,&nbsp;Sara Vinciguerra,&nbsp;Michele Tebaldi,&nbsp;Takshashila Tripathi,&nbsp;Isabella Pesce,&nbsp;Valeria Poli,&nbsp;Alessandro Romanel,&nbsp;Rosario Moratalla,&nbsp;Thierry Voet,&nbsp;Jasmin Morandell,&nbsp;Remo Sanges,&nbsp;Vanessa C. Wheeler,&nbsp;Erik Dassi,&nbsp;Marta Biagioli","doi":"10.1111/bpa.70135","DOIUrl":"10.1111/bpa.70135","url":null,"abstract":"<p>Understanding the molecular mechanisms driving selective neuronal vulnerability to different neurodegenerative disorders remains a crucial, unsolved question. Here, we explored the case of Huntington's disease (HD), where the striatum and, specifically, dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) medium-sized spiny neurons (MSNs) exhibit differential susceptibility to the <i>HTT</i> CAG-repeat expansion mutation, with D2R-neurons being impacted earlier and more significantly. To unravel differences between D2R and D1R MSNs, we employed a multidimensional approach, integrating genomic, transcriptional, pattern distribution, and somatic instability analyses. Specifically, we used <i>Htt</i> CAG knock-in mouse models harboring 18 (<i>Htt</i>^<i>Q20</i>: “control”) or ~190 (<i>Htt</i>^<i>Q175</i>: “HD”) consecutive CAG repeats, expressing tdTomato and EGFP under the control of <i>Drd1</i> and <i>Drd2</i> promoters, respectively. First, comprehensive genomic and transcriptomic analyses following fluorescence-activated cell sorting (FACS) of dissociated striatal neurons revealed distinct gene expression profiles with a significant upregulation of oxidative phosphorylation and translation pathways in D1R-positive neurons already at the pre-symptomatic stage. These transcriptional changes were not accompanied by major copy number variations, as shown by parallel genomic analysis. Secondly, histological analyses revealed a greater proportion of D1R-positive neurons compared to D2R-positive neurons in HD mice, particularly in the ventral-medial neostriatum, with D2R-positive neurons presenting an increased nuclear accumulation of mutant huntingtin aggregates. In summary, our integrative study suggests that the distinct vulnerability of MSNs in HD might result from a combination of an early transcriptional compensatory response of D1R neurons together with specific susceptibility of D2R neurons.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817589","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":"Patient-derived surgical samples reveal the cellular and molecular signatures of glioblastoma infiltration in distinct radiological zones","authors":"Olaya de Dios,&nbsp;Juan Romero,&nbsp;María de los Ángeles Ramírez-González,&nbsp;Beatriz Herranz,&nbsp;Alicia Avis-Bodas,&nbsp;Juliana Manosalva,&nbsp;Diego Megías,&nbsp;Ana Ramos,&nbsp;Juan Manuel Sepúlveda-Sánchez,&nbsp;Ricardo Gargini,&nbsp;Berta Segura-Collar,&nbsp;Gabriel Velilla,&nbsp;Bárbara Meléndez,&nbsp;Pedro González,&nbsp;Luis Jiménez-Roldán,&nbsp;Guillermo García-Posadas,&nbsp;Aurelio Hernández-Laín,&nbsp;Ángel Pérez-Núñez,&nbsp;Pilar Sánchez-Gómez","doi":"10.1111/bpa.70106","DOIUrl":"10.1111/bpa.70106","url":null,"abstract":"<p>Glioblastoma (GBM) is one of the deadliest cancers, largely due to its nearly inevitable recurrence driven by residual tumor cells. Recent evidence suggests that performing supratotal resections that extend into non-contrast-enhancing (nCE) tumor regions may prolong survival. However, tumor infiltration in these areas has not been fully characterized. Our goal was to define the cellular landscape of the GBM periphery and its clinical relevance. To accomplish this, we prospectively collected 161 biopsies from 45 GBM patients. The samples were classified using magnetic resonance imaging (MRI) as either enhancing tumor, nCE tumor, vasogenic edema, or radiologically normal tissue. We performed immunohistochemistry with MIB1 staining to detect proliferative cells and measure cell density. We also performed transcriptional profiling, selecting immune, glial, and vascular markers from single-cell RNA sequencing data. We analyzed the associations with the extent of resection and patient outcomes. Most nCE tumor biopsies displayed neoplastic features, including high cellularity, proliferative markers, and loss of oligodendrocyte signatures. However, some regions labeled as edema by MRI also contained infiltrating tumor cells and were associated with disease progression. Therefore, although MRI-based classification of nCE tumor regions is generally accurate, it underestimates infiltration within edema-labeled areas. Furthermore, in patients who underwent gross-total resection, high peripheral cellularity predicted earlier local recurrence. This suggests that assessing cell density in the periphery can improve recurrence risk prediction. Regarding the tumor microenvironment analysis, immune-related phenotypes were associated with a worse prognosis only after complete resection of the enhancing tumor. Furthermore, our gene panel, particularly the oligodendrocyte markers, provides prognostic insights depending on both biopsy location and resection extent. These findings support the integration of histological and molecular evaluations of the tumor periphery into surgical and therapeutic decision-making processes. This approach offers a path to better patient stratification and outcome prediction in GBM.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833964","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":"Comments to the “Letter to the Editor” for the manuscript titled “Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease”","authors":"Juan Pablo de Rivero Vaccari,&nbsp;David A. Davis,&nbsp;Andrew P. Sawaya,&nbsp;Susanna P. Garamszegi,&nbsp;Xiaoyan Sun,&nbsp;Ayled Barreda,&nbsp;Helen M. Bramlett,&nbsp;Sakir Humayun Gultekin,&nbsp;W. Dalton Dietrich,&nbsp;Robert W. Keane,&nbsp;Regina T. Vontell","doi":"10.1111/bpa.70113","DOIUrl":"10.1111/bpa.70113","url":null,"abstract":"<p>Beta amyloid diffuse plaques, neurofibrillary tangles and neuritic plaques, are increased in densities at the intermediate stage of Alzheimer's neuropathological change. These pathological changes releasing Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs). These molecules are sensed by pattern recognition receptors (PRRs) and trigger intracellular responses. One response is the activation of the inflammasome sensors NLRP1, NLRP3, and AIM2 to oligomerize with ASC speck to form the inflammasome complex and initiate the downstream signaling of GSDMD mediated pyroptosis. Another response is the increase in genes to manufacture proinflammatory cytokines, the inflammasome formation activates the cleavage of the proinflammatory cytokines to the activated forms, which are secreted into the extracellular environment and recruit a widespread inflammation\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197306","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}