Journal of Neuropathology and Experimental Neurology最新文献

Correction to: Identification of diagnostic biomarkers for relapsing-remitting multiple sclerosis in plasma by mass spectrometry-based proteomics. 修正：用基于质谱的蛋白质组学鉴定血浆中复发缓解型多发性硬化的诊断性生物标志物。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-07 DOI: 10.1093/jnen/nlag023

引用次数: 0

Leucine-rich pentatricopeptide repeat-containing protein silencing transcriptionally regulated by GATA-binding protein 3 has an anti-glioma effect by regulating glycolysis and ferroptosis by mediating N6-methyladenosine modification of protocadherin-7. gata结合蛋白3转录调控的富亮氨酸五肽重复蛋白沉默，通过介导原钙粘蛋白7的n6 -甲基腺苷修饰，调节糖酵解和铁凋亡，具有抗胶质瘤作用。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-04 DOI: 10.1093/jnen/nlag043

Yong Sun, Yunlong Jia, Xingyao Bu, Yusheng Chen, Ruixing Wang

{"title":"Leucine-rich pentatricopeptide repeat-containing protein silencing transcriptionally regulated by GATA-binding protein 3 has an anti-glioma effect by regulating glycolysis and ferroptosis by mediating N6-methyladenosine modification of protocadherin-7.","authors":"Yong Sun, Yunlong Jia, Xingyao Bu, Yusheng Chen, Ruixing Wang","doi":"10.1093/jnen/nlag043","DOIUrl":"https://doi.org/10.1093/jnen/nlag043","url":null,"abstract":"Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a recently identified N6-methyladenosine (m6A) reader protein involved in a myriad of biological processes in cancer. However, its roles in glioma have not been reported. Both in vitro and in vivo studies were performed to examine the anti-glioma activity of LRPPRC silencing. Chromatin immunoprecipitation assay and RNA immunoprecipitation assay were used for the analysis of interaction between upstream and downstream molecules. Methylated RNA immunoprecipitation assay was conducted to examine m6A modification. Our results showed that LRPPRC expression was dramatically upregulated in glioma tissues and cell lines. LRPPRC regulated the m6A modification of protocadherin-7 (PCDH7) and affected its expression in glioma cell lines; LRPPRC silencing significantly inhibited glycolysis and induced ferroptosis in glioma cell lines; this was reversed by PCDH7 overexpression. Furthermore, GATA-binding protein 3 (GATA3) directly bound to the LRPPRC promoter and transcriptionally regulated LRPPRC. LRPPRC mediated the regulatory effects of GATA3 on glycolysis and ferroptosis in glioma cell lines. In vivo studies showed that LRPPRC silencing suppressed tumor growth. Taken together, our data demonstrate that LRPPRC expression was dramatically upregulated in gliomas and that inhibition of the GATA3/LRPPRC/PCDH7 axis exerted an anti-glioma effect by regulating glycolysis and ferroptosis.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGFR1::TACC1 fusion in mixed-morphology pediatric glioneuronal tumors: Report of two cases. FGFR1::TACC1融合治疗混合形态儿童神经胶质细胞肿瘤：2例报告

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf125

Erva Bengu Balaban Yilmaz, Nese Yeldir, Cansu Sonmez, Asli Cakir, Fugen Vardar Aker

引用次数: 0

Long COVID neuropathy: The role of mast cells. 长冠神经病变：肥大细胞的作用。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlag016

Zachary L Morcos, Theoharis C Theoharides

{"title":"Long COVID neuropathy: The role of mast cells.","authors":"Zachary L Morcos, Theoharis C Theoharides","doi":"10.1093/jnen/nlag016","DOIUrl":"10.1093/jnen/nlag016","url":null,"abstract":"Postacute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is estimated to affect over 60 million individuals globally, with almost half of COVID-19 survivors experiencing persistent symptoms such as neuropathic pain, fatigue, and autonomic dysfunction. Despite its prevalence, the pathophysiology of PASC remains poorly understood. This narrative review highlights activation of mast cells (MCs), the unique tissue immune cells as a central contributor to neuropathic manifestations in PASC. Mast cell locations near nerves and vessels allows them to regulate neuroimmune and neurovascular processes. Mast cell activation mirrors patterns seen in small-fiber neuropathy and myalgic encephalomyelitis/chronic fatigue syndrome, suggesting a shared immune-mediated etiology. The SARS-CoV-2 spike protein has been shown to activate MCs via angiotensin-converting enzyme 2 and toll-like receptor 4, triggering release of pro-inflammatory and neurotoxic mediators, including interleukin-1β, interleukin-6, tumor necrosis factor alpha, histamine, and tryptase. Such mediators sensitize peripheral nerves, disrupt the blood-brain barrier, and recruit microglia, ultimately contributing to small-fiber injury, neuroinflammation, and dysautonomia. Emerging reports suggest benefit from MC-directed treatments although responses remain variable. Understanding the role of MCs in PASC may offer a plausible mechanism of pathogenesis and guide targeted therapies. Future studies are needed to validate these findings and improve PASC patient outcomes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"413-424"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular and clinical prognostic factors in isocitrate dehydrogenase-mutant astrocytomas: Insights into biomarker-driven stratification. 异柠檬酸脱氢酶突变星形细胞瘤的分子和临床预后因素：生物标志物驱动分层的见解。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf154

Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Ryutaro Makino, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Ryosuke Otsuji, Yutaka Fujioka, Ryusuke Hatae, Daisuke Kuga, Shohei Nagasaka, Kohei Suzuki, Junkoh Yamamoto, Koji Yoshimoto, Akihide Tanimoto, Ryosuke Hanaya

{"title":"Molecular and clinical prognostic factors in isocitrate dehydrogenase-mutant astrocytomas: Insights into biomarker-driven stratification.","authors":"Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Ryutaro Makino, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Ryosuke Otsuji, Yutaka Fujioka, Ryusuke Hatae, Daisuke Kuga, Shohei Nagasaka, Kohei Suzuki, Junkoh Yamamoto, Koji Yoshimoto, Akihide Tanimoto, Ryosuke Hanaya","doi":"10.1093/jnen/nlaf154","DOIUrl":"10.1093/jnen/nlaf154","url":null,"abstract":"CDKN2A/B homozygous deletion (HD) defines isocitrate dehydrogenase (IDH)-mutant astrocytomas as World Health Organization (WHO) grade 4 and predicts aggressive tumor behavior. To identify clinical and molecular prognostic factors in these tumors, we conducted a retrospective multi-institutional study of 106 adult patients diagnosed with IDH-mutant astrocytomas (21 grade 2, 40 grade 3 and 45 grade 4). Tumors were classified using a custom DNA/RNA next-generation sequencing panel based on the 2021 WHO classification. This resulted in an upgrade to grade 4 in 10.3% of cases previously classified as grade II or III due to CDKN2A/B HD. Multivariate analysis identified CDKN2A/B HD (hazard ratio [HR], 1.76; P = .005), MET fusions/splicing variants (HR, 5.38; P = .002), and PDGFRA alterations (HR, 3.66; P = .009) as independent predictors for poor overall survival. The accumulation of these 3 genetic events was strongly associated with unfavorable survival (P < .001) and correlated with adverse clinical features, including lower Karnofsky Performance Status and higher Ki-67 indices. Our study validates the prognostic value of the WHO 2021 classification for IDH-mutant astrocytomas and demonstrates that MET and PDGFRA alterations are independent adverse prognostic factors, comparable to CDKN2A/B HD. Their cumulative burden enables refined molecular risk stratification to guide clinical management.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"455-463"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinicopathological study of chronic traumatic encephalopathy pathology in a population-based cohort. 慢性创伤性脑病病理在人群队列中的临床病理研究。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf150

Roberta Diehl Rodriguez, Christopher Nowinski, Claudia Kimie Suemoto, Renata Elaine P Leite, Renata Eloah de Lucena Ferretti-Rebustini, Wilson Jacob-Filho, Carlos Augusto Pasqualucci, Ricardo Nitrini, Lea T Grinberg

{"title":"Clinicopathological study of chronic traumatic encephalopathy pathology in a population-based cohort.","authors":"Roberta Diehl Rodriguez, Christopher Nowinski, Claudia Kimie Suemoto, Renata Elaine P Leite, Renata Eloah de Lucena Ferretti-Rebustini, Wilson Jacob-Filho, Carlos Augusto Pasqualucci, Ricardo Nitrini, Lea T Grinberg","doi":"10.1093/jnen/nlaf150","DOIUrl":"10.1093/jnen/nlaf150","url":null,"abstract":"Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease linked to repetitive traumatic brain injury, but its prevalence and risk factors in the general population remain poorly defined. We investigated CTE neuropathological changes (CTE-NC) in an admixed, population-based clinicopathological cohort. Neuropathological evaluation was conducted on brain samples from 1151 individuals in the University of São Paulo Biobank for Aging Studies collected from 2004 to 2022. CTE-NC and aging-related tau astrogliopathy (ARTAG) were assessed across 14 963 histological slides using p-tau immunostaining. Clinical, cognitive, and neuropsychiatric data were obtained via informant interviews; information on sports exposure and traumatic brain injury history was limited. Seven cases (0.6%) met criteria for CTE-NC, mean age at death 73.4 ± 12.5 years; 1 was female. Dementia was present in 43% of CTE-NC cases; 57% exhibited neuropsychiatric symptoms. Most common co-pathologies were Alzheimer disease-type changes, ARTAG, and argyrophilic grain disease. Comprehensive exposure histories were unavailable for most cases; 2 had documented soccer involvement. These findings indicate that CTE-NC is rare in this population-based Brazilian cohort and predominantly affects males with frequent coexisting neuropathologies. Findings align with reports from high-income countries and support prioritizing primary prevention by reducing exposure to repetitive head impacts in sport and other settings.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"425-432"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantification of Ki-67 labeling index in pediatric brain tumor immunohistochemistry images. 儿童脑肿瘤免疫组化图像Ki-67标记指数的定量分析。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf163

Christoforos Spyretos, Juan Manuel Pardo Ladino, Hakon Andersen Blomstrand, Per Nyman, Oscar Snödahl, Alia Shamikh, Nils Elander, Neda Haj-Hosseini

{"title":"Quantification of Ki-67 labeling index in pediatric brain tumor immunohistochemistry images.","authors":"Christoforos Spyretos, Juan Manuel Pardo Ladino, Hakon Andersen Blomstrand, Per Nyman, Oscar Snödahl, Alia Shamikh, Nils Elander, Neda Haj-Hosseini","doi":"10.1093/jnen/nlaf163","DOIUrl":"10.1093/jnen/nlaf163","url":null,"abstract":"Quantification of the Kiel 67 (Ki-67) labeling index (LI) is critical for assessing proliferation and prognosis in tumors but manual scoring remains a common practice. We present an automated framework for Ki-67 scoring in whole slide images (WSIs) developed for research settings using an Apache Groovy code script for QuPath and complemented by a Python postprocessing script that provides cell density maps and summary tables. Tissue segmentation is performed by pixel classifiers and cell segmentation is conducted using StarDist, a deep learning model, followed by adaptive thresholding to classify Ki-67 positive and negative nuclei. The pipeline was applied to a cohort of 632 pediatric brain tumor cases with 734 Ki-67 WSIs from the Children's Brain Tumor Network. Medulloblastomas showed the highest Ki-67 LI (median: 19.84), followed by atypical teratoid rhabdoid tumors (median: 19.36), brainstem glioma-diffuse intrinsic pontine gliomas (median: 11.50), high-grade gliomas (grades 3, 4) (median: 9.50), and ependymomas (median: 5.88). Lower indices were found in meningiomas (median: 1.84) and the lowest were seen in low-grade gliomas (grades 1, 2) (median: 0.85), dysembryoplastic neuroepithelial tumors (median: 0.63), and gangliogliomas (median: 0.50). The results demonstrate a significant correlation (P < .05) in Ki-67 LI across most of the tumor families/types aligning with neuro-oncology and neuropathology consensus.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"475-486"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-grade diffusely infiltrative tumor, SMARCB1-mutant: A diagnostic challenge-case report. 低级别弥漫性浸润性肿瘤，smarcb1突变体：一个诊断挑战病例报告。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf124

Takahiro Miyazaki, Yuhei Sangatsuda, Hirokazu Sugino, Satoshi Nakata, Ayako Yamazaki, Takako Yoshioka, Junko Hirato, Satoshi O Suzuki, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Masahiro Mizoguchi, Sumihito Nobusawa, Koji Yoshimoto

引用次数: 0

Cardiotrophin-like cytokine factor 1 regulated by Sry-related HMG-box transcription factor 9 promotes malignant behavior and immune evasion of glioblastoma multiforme. sry相关HMG-box转录因子9调控的心营养因子样细胞因子1促进多形性胶质母细胞瘤的恶性行为和免疫逃避。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf161

Jiangwei Yuan, Haiying Liu, Junpeng Wen, Zhenxiang Zhao, Yaqi Peng, Yingzi Liu

{"title":"Cardiotrophin-like cytokine factor 1 regulated by Sry-related HMG-box transcription factor 9 promotes malignant behavior and immune evasion of glioblastoma multiforme.","authors":"Jiangwei Yuan, Haiying Liu, Junpeng Wen, Zhenxiang Zhao, Yaqi Peng, Yingzi Liu","doi":"10.1093/jnen/nlaf161","DOIUrl":"10.1093/jnen/nlaf161","url":null,"abstract":"Cardiotrophin-like cytokine factor 1 (CLCF1) is an unfavorable factor for the prognosis of patients with glioblastoma multiforme (GBM). This research explored the functions of CLCF1 in GBM progression and the underlying regulatory mechanisms. Reverse transcription-quantitative PCR (RT-qPCR) and Western blot were used to detect the mRNA and protein levels of targeted molecules. The abilities of GBM cell lines to proliferate, migrate, and invade and undergo apoptosis and angiogenesis were analyzed by colony formation, transwell, TUNEL, and tube formation assays, respectively. Interaction between CLCF1 and SRY-box transcription factor 9 (SOX9) was verified by chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays. The results showed that CLCF1 was upregulated in GBM. Silencing of CLCF1 suppressed the malignant phenotypes of GBM cells in vitro and the development of GBM in a xenograft tumor model. Silencing CLCF1 also reduced programmed cell death 1 ligand 1 (PD-L1) expression in GBM cells and prolonged the longevity of CD8-positive T cells in vitro. SRY-box transcription factor 9 was highly expressed in GBM and this activated CLCF1 expression as one of its transcription factors to further enhance GBM development. Thus, CLCF1 regulated by SOX9 can enhance the development and immune evasion of GBM.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"496-506"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing Gallyas and AT8 staining for quantification of tau pathology in subregions of the human hippocampus. 比较Gallyas和AT8染色定量测定人海马亚区tau病理。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-01 DOI: 10.1093/jnen/nlaf149

Bayla Breningstall, Evan Abdollahi, Debra Hawes, Annie Hiniker, Michael S Bienkowski

{"title":"Comparing Gallyas and AT8 staining for quantification of tau pathology in subregions of the human hippocampus.","authors":"Bayla Breningstall, Evan Abdollahi, Debra Hawes, Annie Hiniker, Michael S Bienkowski","doi":"10.1093/jnen/nlaf149","DOIUrl":"10.1093/jnen/nlaf149","url":null,"abstract":"Gallyas silver staining and AT8 immunostaining are frequently used to stage tau pathology in post-mortem Alzheimer disease (AD) brains. Because of differential labeling of tau aggregation types, however, these methods result in strikingly different patterns of pathology when used in adjacent sections of the same brain. How Gallyas versus AT8 staining impacts the quantification of tau pathology distribution across brain areas and affect analysis of tau and cognitive impairment is unknown. We performed a side-by-side comparison of AT8 versus Gallyas-stained hippocampal sections from 34 patients from the University of Southern California (USC) Alzheimer's Disease Research Center (ADRC). Using images of Gallyas and AT8 stained sections, we computed overall tau density in hippocampal subregions as well as manual tangle counts and compared each of them to cognitive variables like Clinical Dementia Rating and Mini Mental State Exam in the patients. We found that AT8 had a much higher density of staining overall, and the two stains had differing distributions, with increased AT8 in Brodmann area 35 and CA1. Both stains related to cognition differentially, and Gallyas density was significantly related to post-mortem interval. These findings contribute to our understanding of how tau pathology stain choice might influence the characterization of AD.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"433-445"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0