Brain Pathology最新文献

{"title":"Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup-specific prognostic stratification using economical/accessible diagnostic methods","authors":"Kohichi Go,&nbsp;Asako Katsuma,&nbsp;Ema Yoshioka,&nbsp;Tomoko Shofuda,&nbsp;Kohei Fukuoka,&nbsp;Koichi Ichimura,&nbsp;Yuko Matsushita,&nbsp;Yohei Mineharu,&nbsp;Yasuhide Makino,&nbsp;Takeshi Kawauchi,&nbsp;Atsushi Sasaki,&nbsp;Junko Hirato,&nbsp;Takeshi Inoue,&nbsp;Yoshinori Kodama,&nbsp;Masayuki Mano,&nbsp;Daisuke Kanematsu,&nbsp;Noriyuki Kijima,&nbsp;Naoki Kagawa,&nbsp;Dai Keino,&nbsp;Akitake Mukasa,&nbsp;Tomonari Suzuki,&nbsp;Koji Yoshimoto,&nbsp;Daisuke Kuga,&nbsp;Keishi Horiguchi,&nbsp;Shigeru Yamaguchi,&nbsp;Masayuki Kanamori,&nbsp;Kai Yamasaki,&nbsp;Kenichi Ishibashi,&nbsp;Takuya Akai,&nbsp;Masayoshi Yamaoka,&nbsp;Ryuji Ishizaki,&nbsp;Atsufumi Kawamura,&nbsp;Shigeo Ohba,&nbsp;Joji Ishida,&nbsp;Ryo Ando,&nbsp;Junya Fukai,&nbsp;Tomoru Miwa,&nbsp;Masazumi Fujii,&nbsp;Ai Muroi,&nbsp;Kuniaki Saito,&nbsp;Atsuko Harada,&nbsp;Yasuhiko Hayashi,&nbsp;Masahiro Nonaka,&nbsp;Young-Soo Park,&nbsp;Yusuke Kobayashi,&nbsp;Tadashi Higuchi,&nbsp;Yosuke Miyairi,&nbsp;Kazuhisa Yoshifuji,&nbsp;Noriyoshi Takebe,&nbsp;Soichi Oya,&nbsp;Kosuke Nakajo,&nbsp;Mitsutoshi Nakada,&nbsp;Yoshiteru Nakano,&nbsp;Mizuki Kambara,&nbsp;Koji Adachi,&nbsp;Kazuhiro Tanaka,&nbsp;Hideo Nakamura,&nbsp;Yukihiko Sonoda,&nbsp;Ryuta Saito,&nbsp;Takafumi Wataya,&nbsp;Kazuhiko Kurozumi,&nbsp;Michael D. Taylor,&nbsp;Yoshitaka Narita,&nbsp;Soichiro Shibui,&nbsp;Hajime Arai,&nbsp;Hiroaki Sakamoto,&nbsp;Isao Date,&nbsp;Motoo Nagane,&nbsp;Ryo Nishikawa,&nbsp;Yoshiki Arakawa,&nbsp;Yonehiro Kanemura","doi":"10.1111/bpa.70092","DOIUrl":"10.1111/bpa.70092","url":null,"abstract":"<p>Medulloblastoma (MB) is a biologically and clinically heterogeneous pediatric brain tumor. However, large-scale molecular subgrouping studies have mainly been conducted in Western populations, and comprehensive data from Asia are limited. To address this gap, we analyzed 242 MB cases collected from 39 institutions through the Japan Pediatric Molecular Neuro-Oncology Group, performing centralized molecular classification using NanoString-based gene expression profiling, DNA methylation arrays, and multiplex ligation-dependent probe amplification (MLPA)-based copy number profiling, supplemented by targeted sequencing. The subgroup distribution was 16.1% WNT, 24.8% SHH, 17.4% Group 3, and 41.7% Group 4. <i>CTNNB1</i> mutations and monosomy 6 characterized all WNT cases, whereas <i>MYCN</i> amplification and <i>TP53</i> mutations were independent adverse markers in SHH MB. Group 3 showed the worst survival, with <i>MYC</i> amplification and metastasis as poor prognostic factors. In Group 4, large cell/anaplastic histology predicted poor outcomes, whereas chromosome 11 loss was correlated with a favorable prognosis. Whole chromosomal aberration-defined favorable-risk patterns consistently indicate improved outcomes in non-WNT/non-SHH MBs. We also developed a simplified MLPA-based classifier targeting six loci on chromosomes 7, 8, and 11 (SEE-6-CNA), which enabled robust and clinically feasible prognostic stratification. Overall, our findings confirm that the molecular subgroup-specific features of Japanese MBs are largely concordant with global observations and that SEE-6-CNA provides a cost-effective tool to support individualized treatment planning, particularly in resource-limited settings.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430475","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":"Proteomic profile of CSF obtained at the time of diagnosis determines amyotrophic lateral sclerosis progression and survival: CXCL7 levels in disease prognosis and survival","authors":"Sergio Roca-Pereira,&nbsp;Yaiza López-Sampere,&nbsp;Pol Mengod-Soler,&nbsp;Mario Peña-Fonteboa,&nbsp;Carla Marco,&nbsp;Alejandro Caravaca-Puchades,&nbsp;Raúl Domínguez,&nbsp;Juan Francisco Vázquez-Costa,&nbsp;Enrique Santamaría,&nbsp;Joaquín Fernández-Irigoyen,&nbsp;María J. Colomina,&nbsp;Isabel León Moreno,&nbsp;Antonio Martínez Yélamos,&nbsp;Sergio Martínez Yélamos,&nbsp;Gabriel Santpere,&nbsp;Elia Obis,&nbsp;Manuel Portero-Otín,&nbsp;Gerard Piñol-Ripoll,&nbsp;Mónica Povedano,&nbsp;Pol Andrés-Benito","doi":"10.1111/bpa.70089","DOIUrl":"10.1111/bpa.70089","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Neurofilament light chain (NfL) is the most established prognostic biomarker; however, its diagnostic resolution is limited, particularly within intermediate concentration ranges, and it does not capture the molecular heterogeneity of ALS. This study aimed to identify complementary cerebrospinal fluid (CSF) biomarkers and pathway-specific signatures through a non-targeted multiomic approach. We performed SWATH-MS-based proteomics and LC–MS/MS lipidomics on CSF from ALS patients stratified by survival (ALS-SS and ALS-LS) and healthy controls. Weighted protein co-expression network analysis (WPCNA) was applied to identify biologically coherent protein modules associated with disease phenotype and progression. Top biomarker candidates were further evaluated using immunoassays in an independent cohort. Post-mortem ALS spinal cord tissues were analyzed to explore the pathophysiological relevance of identified proteins. CSF proteomic profiles robustly distinguished ALS patients from controls and stratified patient subgroups by survival, revealing a molecular signature characterized by inflammation, downregulation of detoxification mechanisms, and synaptic dysregulation in aggressive disease forms. In contrast, lipidomic profiles showed limited discriminatory power. WPCNA identified modular proteomic signatures capturing ALS heterogeneity, and machine learning models based on these profiles yielded optimal biomarker panels for diagnosis and prognosis. CXCL7 emerged as a promising complementary biomarker, and shed light in disease physiopathology. Immunoassay validation supported the diagnostic and prognostic potential of CXCL7 and its association with survival time. Histopathological analysis further confirmed CXCL7 localization in anterior horn motor neurons, despite no detectable changes in whole spinal cord lysates at late disease stages. Comprehensive CSF proteomic profiling, combined with network-based analysis, enhances our understanding of ALS molecular heterogeneity and provides a framework for precision biomarker discovery. CXCL7 complements NfL as a diagnostic and prognostic biomarker, supporting improved patient stratification and advancing the development of personalized therapeutic strategies in ALS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347196","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":"From patient to tumor organoid: Culture protocol choice controls glioblastoma tumor architecture and identity.","authors":"Jana Slovackova, Ondrej Bernatik, Katarina Cimborova, Martin Barak, Michal Hendrych, Karolina Kocourkova, Marie Sulcova, Jaroslav Olha, Katerina Amruz Cerna, Zdenek Hodny, Radim Jancalek, Dasa Bohaciakova","doi":"10.1111/bpa.70125","DOIUrl":"10.1111/bpa.70125","url":null,"abstract":"<p><p>Patient-derived tumor organoids are widely used in cancer research, yet the biological impact of tissue processing during model generation remains unclear. Fragment-based and dissociation-based (DIS) approaches are commonly assumed to trade fidelity for uniformity, but their molecular consequences remain incompletely defined. To address this gap, we performed a proteome-wide comparison of fragment-based (cut-and-culture [CUT]) and DIS glioblastoma organoid protocols using quantitative mass spectrometry. Organoids from multiple patient tumors were cultured under growth factor-free or growth factor-supplemented conditions and compared with matched primary tissue. Results show that both protocols produced technically robust glioblastoma organoids when maintained in their native media. However, CUT organoids matched the reproducibility of DIS cultures while preserving a broader extracellular matrix (ECM) repertoire and networks linked to collagen assembly, vascular support, and cell-matrix signaling. DIS cultures were biased toward exogenous basement membrane components and proliferative, growth factor-responsive states. Across tumors, CUT organoids consistently showed greater proteomic similarity to matched primary tissue, retaining neural, glial, stromal, and extracellular features largely absent from DIS models. Taken together, fragment-based glioblastoma organoids can be both reproducible and biologically faithful. Tissue dissociation acts as a major perturbation that reshapes ECM organization, cellular states, and tumor identity, making protocol choice a critical determinant of model fidelity and translational relevance.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70125"},"PeriodicalIF":5.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590443","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":"A novel myopathy with autophagic vacuoles associated with biallelic variants in CLN8.","authors":"Ulrika Lindgren, Carola Hedberg-Oldfors, Kittichate Visuttijai, Sara Nordström, Hans Goebel, Anders Oldfors","doi":"10.1111/bpa.70128","DOIUrl":"10.1111/bpa.70128","url":null,"abstract":"<p><p>Autophagic vacuoles in muscle fibers are a characteristic finding in several muscle diseases and usually indicate perturbed lysosomal protein degradation. Some of these are associated with defects in proteins directly involved in autophagy and lysosomal degradation. The gene CLN8 encodes an endoplasmic reticulum transmembrane protein, previously associated with childhood-onset neuronal ceroid lipofuscinosis (NCL), a group of lysosomal storage diseases. We describe the clinical features and results from pathology, genetic, and proteomic investigations in an adult-onset myopathy with autophagic vacuoles associated with biallelic variants in CLN8. A 40-year-old woman presented with seizures followed by transient muscle weakness and myalgia. Creatine kinase and myoglobin levels were moderately elevated. Over time, she developed progressive muscle weakness and cognitive fatigue. Muscle biopsy showed an autophagic vacuolar myopathy with fat tissue replacement and increased interstitial connective tissue. There was a marked immunohistochemical increase of markers of autophagy such as lysosomal-associated membrane protein 2 (LAMP2), microtubule-associated protein 1A/1B-light chain 3 (LC3), and sequestosome1/p62, as well as lysosomal deposition of curvilinear-like, autofluorescent material containing subunit c of mitochondrial adenosine triphosphate (ATP) synthase (mitochondrial ATP synthase membrane subunit c locus 3 [ATP5MC3/SCMAS]), typical for some forms of NCLs, including CLN8. Blood lymphocytes showed typical fingerprint inclusions. Genetic analysis revealed biallelic CLN8 variants, c.511C>T; p.P171S and c.536T>A; p.L179H. Proteomic analysis demonstrated upregulation of proteins involved in autophagy, muscle regeneration, and protein turnover. Proteins associated with oxidative phosphorylation were downregulated, except for ATP5MC3/SCMAS, which showed accumulation. In conclusion, we describe a novel myopathy with autophagic vacuoles and characteristic features of ceroid lipofuscinosis, including autophagosomal/lysosomal deposition of curvilinear-like, autofluorescent material containing ATP5MC3/SCMAS. This disease appears to be an unusual adult-onset form of CLN8.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70128"},"PeriodicalIF":5.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590510","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":"The immunological landscape of the area postrema in neuromyelitis optica spectrum disorders.","authors":"Qian Yu, Yoshiki Takai, Naoya Yamazaki, Sarah Brandl, Katharina M Mair, Thibault Bouderlique, Maria Eleni Kastriti, Igor Adameyko, Romana Höftberger, Markus Reindl, Jan Bauer, Monika Bradl","doi":"10.1111/bpa.70127","DOIUrl":"10.1111/bpa.70127","url":null,"abstract":"<p><p>Patients suffering from aquaporin-4 antibody-positive neuromyelitis spectrum disorder may present with radically different types of lesions in the central nervous system. They may show large tissue destructive lesions, as typically seen in medulla, spinal cord, and optic nerves, and lesions with much better tissue preservation, as seen in the area postrema. The causes for the resilience of the area postrema to the action of aquaporin 4-antibodies are currently unclear. We performed detailed immunohistochemical analysis combined with spatial transcriptomics and functional annotation clustering, and identified key differences in the immunological landscape between the area postrema and the medulla. In the area postrema, only few chemokines were upregulated in response to AQP4 antibodies. Therefore, the immune response was dominated by local microglial/macrophages which displayed a low grade of microgliosis and an overall low level of activation. Il-1β expression was below our cut-off for detection. This was in marked contrast to lesions in the medulla, which were characterized by the expression of many chemokines underlying the recruitment of macrophages and neutrophils from the periphery to this site, and by Il-1β expression. Aldehyde dehydrogenase 1 family member A2 (Aldh1a2), the key molecule for retinoic acid synthesis, was strongly expressed in the area postrema, but not in the medulla. Because retinoic acid can prevent the activation of astrocytes and microglia, can reduce the production of cytokine/chemokine transcripts, can alleviate the expression of IL-1β, and can promote an M1- to M2-transition in macrophages, our data implicate a protective role of retinoic acid at this site.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70127"},"PeriodicalIF":5.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590460","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":"ALT phenotype assessment in IDH-mutant astrocytoma supports biologic consequence of ATRX missense mutations.","authors":"Oguzhan O Kizilkaya, Kevin Y Zhang, Mohamed Sherief, Debraj Mukherjee, Chetan Bettegowda, Matthias Holdhoff, Victoria Croog, Solmaz Sahebjam, David O Kamson, Jordina Rincon-Torroella, Karisa C Schreck, Charles G Eberhart, Alan Meeker, Calixto-Hope G Lucas","doi":"10.1111/bpa.70126","DOIUrl":"https://doi.org/10.1111/bpa.70126","url":null,"abstract":"<p><p>A meaningful subset of IDH-mutant astrocytoma harbors ATRX missense variants that retain ATRX IHC immunoreactivity yet exhibit functional ALT activation, supporting the biologic relevance of these missense mutations.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70126"},"PeriodicalIF":5.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577148","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":"Clinicopathological and molecular heterogeneity of amyloid-β in unnatural deaths under 70 years: A forensic autopsy-based study.","authors":"Shojiro Ichimata, Yukiko Hata, Koji Yoshida, Ryo Tanaka, Shigeo Murayama","doi":"10.1111/bpa.70124","DOIUrl":"https://doi.org/10.1111/bpa.70124","url":null,"abstract":"<p><p>This study investigated the clinicopathological characteristics and molecular spectrum of amyloid-beta (Aβ) in unnatural deaths among relatively young individuals with moderate-to-severe Aβ deposition, including cases of early-onset Alzheimer's disease. A total of 856 forensic autopsy cases aged 40-69 years were analyzed. Detailed semiquantitative and quantitative immunohistochemical analyses were performed in the neocortex, striatum (caudate nucleus, putamen, and nucleus accumbens [NAc]), and amygdala using antibodies targeting multiple Aβ species (Aβ38, Aβ39, Aβ40, Aβ42, Aβ43, pyroglutamate-modified Aβ at the third glutamate residue [AβNp3E], and serine 8-phosphorylated Aβ), as well as phosphorylated tau. Ward's hierarchical cluster analysis was also performed. Thirty-three cases (eight females; 3.9%), including six early-onset Alzheimer's disease cases, were identified. Three cases exhibited genetic abnormalities (one with Down syndrome and two with presenilin 1 [PSEN1] mutations). Marked regional heterogeneity in Aβ molecular profiles was observed, particularly within the striatum. Notably, the NAc displayed a distinct pattern of Aβ deposition and occasional NAc-predominant cerebral amyloid angiopathy. Cases with cognitive impairment (CI) demonstrated more advanced Aβ and tau pathology than CI-negative cases; notably, interstitial Aβ42 and Aβ43 burdens were significantly elevated across all regions. Strikingly, siblings carrying the same PSEN1 mutation-one with CI and the other without-exhibited divergent pathological patterns. Although suicide accounted for approximately one-third of cases, a higher neocortical Aβ burden was associated with a lower frequency of suicide, and no significant difference in suicide rates was observed compared with cases lacking substantial Aβ deposition. Cluster analysis identified a subgroup characterized by relatively elevated striatal Aβ deposition, particularly AβNp3E. Collectively, these findings indicate that the severity of Aβ deposition is not directly associated with suicide. However, early involvement of the NAc may contribute to depressive states, and region-specific Aβ species-particularly Aβ42, Aβ43, and AβNp3E-may be associated with increased cognitive vulnerability in this age group.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70124"},"PeriodicalIF":5.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469332","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":"Interlaboratory performance testing on EPIC v2.0 CNS tumor profiling demonstrates high reproducibility of tumor classification but reveals the need for harmonized copy number variation reporting.","authors":"Katrin Mauch-Mücke, Christin Siewert, Lora Dimitrova, Sandra Pohl, Brendan Osberg, Annika K Wefers, Julia Lorenz, Tanja Rothhammer-Hampl, Till Acker, Alonso Barrantes-Freer, Jean Boutonnat, Bérengère Dadone-Montaudié, Claire Delbridge, Wolfgang Dietmaier, Sebastian Dintner, Hildegard Dohmen, Matthias Dottermusch, Daniel Erny, Katrin B M Frauenknecht, Tobias Goschzik, Patrick N Harter, Daniela Hirsch, Yanghao Hou, Theo F J Kraus, Maggie Lee, Friederike Liesche-Starnecker, Anne Mc Leer, Linea Melchior, Michael Mittelbronn, Wolf C Müller, Shalima S Nair, Julia E Neumann, Pitt Niehusmann, Nicole Pfarr, Torsten Pietsch, Marco Prinz, Markus Rechsteiner, Regina Reimann, Laveniya Satgunaseelan, Veronica Skarpeteig, Anne J Skjulsvik, Karl Sotlar, Isabelle Vanden Bempt, Erik Vassella, Katharina J Weber, Gabriel Wasinger, Andreas Waha, Karen Zwaenepoel, Felix Sahm, Markus J Riemenschneider, David Capper","doi":"10.1111/bpa.70121","DOIUrl":"https://doi.org/10.1111/bpa.70121","url":null,"abstract":"<p><p>BeadChip array-based DNA methylation profiling has been recognized by the World Health Organization (WHO) as a key diagnostic tool for brain tumor classification. While its diagnostic utility has been well established, data on technical reproducibility, interlaboratory comparability, and data interpretation under real-world diagnostic conditions remain limited. Bridging this gap, we here report the results of an international proficiency test using the Infinium MethylationEPIC v2.0 platform and the corresponding Brain Tumor Classifier version 12.8. Tissue slides of eight FFPE brain tumor samples, covering a representative range of CNS tumor entities, were distributed among 24 laboratories in 10 different countries. Participants were asked to report methylation classes and copy number variation (CNV) profiles. Pre-array workflows were left to local procedures and results had to be submitted within 15 working days. Technical data reproducibility was high with a median pairwise beta-value correlation of 0.99 (range 0.93-1.0). In general, participating centers generated high-quality data, reflected by consistently low detection p-values (<0.01). Eighteen of the 24 participating centers (75%) successfully passed the test. Of the six centers that failed the test, two laboratories experienced technical issues that led to misclassification of individual cases and contributed to incorrect CNV reporting. Four additional centers showed substantial discrepancies in the interpretation of diagnostically highly relevant CNVs, whereas methylation classification was not impaired. While accurate DNA quantification proved to be an important pre-array step, the use of the DNA restoration kit had only minor influence on overall results. Taken together, our interlaboratory performance testing on EPIC v2.0 CNS tumor profiling confirms high reproducibility of tumor classification but reveals the need for harmonized CNV reporting.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70121"},"PeriodicalIF":5.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454749","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":"Non-Alzheimer Aβ deposits in the human CNS: Implications with hypoxia and related conditions.","authors":"Esma Karlovich, David S Priemer, Charles Harker Rhodes, Daniel P Perl, Kurenai Tanji, James E Goldman","doi":"10.1111/bpa.70120","DOIUrl":"https://doi.org/10.1111/bpa.70120","url":null,"abstract":"<p><p>We recently reported the deposition of Aβ in the frontal cortex of individuals who died of acute coronavirus disease 2019 (COVID-19), or who did not have COVID-19 but had respiratory distress, or infants with severe cardiac malformations. These Aβ deposits were not the senile, neuritic core \"plaques\" of Alzheimer's disease (AD) and did not stain for Thioflavin-S or with antibodies to phosphorylated tau protein. Here, we examined multiple sections of the brains of such individuals, finding these non-Alzheimer Aβ deposits (NADAs) predominantly in the isocortex, including frontal, temporal, insular, and occipital, but also in subcortical structures such as the diencephalon, cerebellum, brainstem, and spinal cord, albeit many fewer. NADAs also appeared around blood vessels and within blood vessel walls, but did not incite an inflammatory response. We also examined brains of individuals with metabolic and mitochondrial diseases that lead to hypoxic damage and one individual with severe hyperthermia. All had NADAs identical to the ones we previously reported. These Aβ deposits somewhat resemble the amorphous or diffuse plaques or deposits that have been thought to be associated with early stages of AD, but they are morphologically distinguishable and appear in brains of young individuals who have no Alzheimer pathology. We suggest that the deposits are associated with hypoxia or related mechanisms of injury.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70120"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366809","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":"Distinctly altered TRPC3 and TRPC6 expression patterns in human Alzheimer's disease cortex and hippocampus.","authors":"Xingyong Chen, Zhengjun Wang, Jiaxing Wang, Dehui Kong, Xusheng Wang, Lu Lu, Peter T Nelson, Fu-Ming Zhou, Francesca-Fang Liao","doi":"10.1111/bpa.70118","DOIUrl":"10.1111/bpa.70118","url":null,"abstract":"<p><p>Calcium dysregulation is increasingly recognized as a convergent mechanism underlying neuronal vulnerability and glial overactivation in Alzheimer's disease (AD). Transient Receptor Potential Canonical (TRPC) channels are potential key modulators of Ca²⁺ signaling in multiple cell types in central nervous system (CNS), mediating different pathophysiological roles. However, their cell type-specific remodeling and cellular origins of these changes in human AD tissue remain poorly defined. This study investigated their expression patterns with main focus on the two closely related members of TRPC3 and TRPC6 across human AD brains and two relevant mouse models. Formalin-fixed paraffin-embedded cortical and hippocampal tissues from AD patients and age-matched controls were examined using immunohistochemistry. Spatial relationships between TRPC3/TRPC6 and glial fibrillary acidic protein (GFAP)-positive astrocytes were assessed in adjacent serial sections. TRPC3 expression was markedly increased in AD cortex and hippocampus whereas TRPC6 was significantly reduced primarily in pyramidal neurons. TRPC3-positive regions showed close spatial correspondence with reactive astrocytes, particularly in the hippocampal and subcortical white matter regions, suggesting a partial astrocytic origin. TRPC6 exhibited negligible overlap with GFAP. These observations were reproduced in brain sections of both 5xFAD and PS19 transgenic (Tg) mice compared to their littermate controls. Our findings reveal a conserved pattern of divergent TRPC remodeling across human and mouse models with AD pathology. In addition, TRPC1 expression was significantly reduced in AD samples while TRPC4 and TRPC5 had no significant change in expression. Taken together, selected TRPC family members may undergo differential remodeling during AD pathogenesis, with TRPC3 and TRPC6 showing the most prominent and consistent alterations.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70118"},"PeriodicalIF":5.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350776","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}