Journal of Neuropathology and Experimental Neurology最新文献

Pellagra encephalopathy in Huntington disease: An autopsy case. 亨廷顿病的糙皮病脑病：一个尸检病例。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-10-10 DOI: 10.1093/jnen/nlag109

Hideyuki Moriyoshi, Yuma Hayakawa, Akio Akagi, Yuichi Riku, Jun Sone, Hiroaki Miyahara, Masahisa Katsuno, Hirotaka Nakanishi, Yasushi Iwasaki

引用次数: 0

Persistent JC virus replication despite combined mirtazapine and mefloquine therapy: An autopsy case of progressive multifocal leukoencephalopathy with diffuse large B-cell lymphoma. 尽管米氮平和甲氟喹联合治疗，持续的JC病毒复制：一个进展性多灶性白质脑病伴弥漫性大b细胞淋巴瘤的尸检病例。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-10-08 DOI: 10.1093/jnen/nlag105

Kento Seko, Yuya Kano, Yuto Uchida, Kentaro Yamada, Koji Takada, Mari Yoshida, Kazuo Nakamichi, Noriyuki Matsukawa

引用次数: 0

Somatic PIK3CA and PTEN mutations with endothelial PI3K/AKT/mTOR activation in RAS-negative brain arteriovenous malformations. 体细胞PIK3CA和PTEN突变与内皮PI3K/AKT/mTOR激活在ras阴性脑动静脉畸形中。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-10-01 DOI: 10.1093/jnen/nlag054

Yukiko Hata, Ryo Tanaka, Shojiro Ichimata, Satoshi Kuroda, Naoki Nishida

{"title":"Somatic PIK3CA and PTEN mutations with endothelial PI3K/AKT/mTOR activation in RAS-negative brain arteriovenous malformations.","authors":"Yukiko Hata, Ryo Tanaka, Shojiro Ichimata, Satoshi Kuroda, Naoki Nishida","doi":"10.1093/jnen/nlag054","DOIUrl":"10.1093/jnen/nlag054","url":null,"abstract":"Somatic mutations affecting endothelial signaling pathways have emerged as important contributors to brain arteriovenous malformations (bAVMs). Although activating mutations in the RAS/MAPK pathway have been frequently reported, alternative molecular mechanisms remain incompletely understood. We describe 2 autopsy-confirmed bAVMs harboring somatic PIK3CA mutations, including one case with a concurrent PTEN alteration. Histologically, both lesions demonstrated typical bAVM architecture without unusual structural features. Immunohistochemical analysis revealed lesion-restricted activation of the PI3K/AKT/mTOR pathway in endothelial cells; adjacent normal vessels were negative. In contrast, ERK phosphorylation was focal and limited; targeted sequencing did not identify pathogenic RAS/MAPK mutations. These findings suggest dominant PI3K pathway activation with secondary or limited MAPK engagement. Variant allele frequencies were interpreted cautiously owing to whole-genome amplification from autopsy-derived tissue. In one case, prior Gamma Knife radiosurgery was considered to have contributed to the findings but histological features of radiation-associated vascular injury were not observed. Together, these findings support molecular heterogeneity in bAVMs and suggest that PIK3CA-driven PI3K pathway activation may contribute to vascular remodeling in RAS-negative lesions. Correlation of molecular alterations with pathway-specific endothelial activation highlights the value of integrated genetic and pathological assessment in bAVMs.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"1117-1123"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592079","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

HOXD12 as an oncofetal protein expressed in WNT-activated medulloblastomas. HOXD12在wnt激活的髓母细胞瘤中作为癌胎蛋白表达。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-29 DOI: 10.1093/jnen/nlag104

Vinny Ha, Allison Shelbourn, Charles Eberhart, Jason Chiang, Brent A Orr, Sonali Arora, Eric C Holland, Nicholas Nuechterlein, Brian R Rood, Drew Pratt, Martha Quezado, Patrick J Cimino

{"title":"HOXD12 as an oncofetal protein expressed in WNT-activated medulloblastomas.","authors":"Vinny Ha, Allison Shelbourn, Charles Eberhart, Jason Chiang, Brent A Orr, Sonali Arora, Eric C Holland, Nicholas Nuechterlein, Brian R Rood, Drew Pratt, Martha Quezado, Patrick J Cimino","doi":"10.1093/jnen/nlag104","DOIUrl":"https://doi.org/10.1093/jnen/nlag104","url":null,"abstract":"Aberrant reactivation of embryonic patterning programs is a hallmark of cancer. We previously identified HOXD12 activation in aggressive oligodendrogliomas, but its broader significance across brain tumors remains unexamined. Here, we evaluated HOXD12 protein expression via immunohistochemistry in 162 primary CNS tumors and 84 brain metastases. HOXD12 expression was significantly enriched in primary CNS tumors over brain metastases (P < .0001). Among primary malignancies, medulloblastoma exhibited the highest HOXD12 expression compared to diffuse gliomas, ependymomas, and meningiomas (P < .0001). Conversely, HOXD12 levels did not vary by diffuse glioma subtype or metastatic site of origin. To resolve subgroup-specific patterns, we integrated whole-genome DNA methylation (n = 1338) and bulk RNA-sequencing (n = 876) datasets across medulloblastoma molecular subgroups. Multi-omic analysis revealed maximal HOXD12 gene body methylation and transcript expression specifically within the WNT-activated medulloblastoma subgroup (P < .0001). These findings demonstrate that HOXD12 reactivation is preferentially associated with primary CNS tumors and is highly pronounced in WNT-activated medulloblastomas. Our results position HOXD12 as a candidate immunohistochemical surrogate for the WNT-activated medulloblastoma subgroup.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081135","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

Cardiovascular risk factors and regional neuropathology in autopsy-confirmed Alzheimer disease. 尸检证实阿尔茨海默病的心血管危险因素和局部神经病理学

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-28 DOI: 10.1093/jnen/nlag081

David Garcia, Hsin-Pei Wang, Naomi Saito, Laurel Beckett, Lawrence S Honig, Charles DeCarli, Robert A Rissman, Andrew F Teich, Dan M Mungas, Lee-Way Jin, Brittany N Dugger

{"title":"Cardiovascular risk factors and regional neuropathology in autopsy-confirmed Alzheimer disease.","authors":"David Garcia, Hsin-Pei Wang, Naomi Saito, Laurel Beckett, Lawrence S Honig, Charles DeCarli, Robert A Rissman, Andrew F Teich, Dan M Mungas, Lee-Way Jin, Brittany N Dugger","doi":"10.1093/jnen/nlag081","DOIUrl":"https://doi.org/10.1093/jnen/nlag081","url":null,"abstract":"Cardiovascular risk factors are implicated in Alzheimer disease (AD) progression and its neuropathological hallmarks but their specific contributions to regional brain pathology within AD remain understudied. In this cohort study (n = 276), we examined associations between diabetes, hypertension, and hypercholesterolemia (present vs absent), and neuropathologies in decedents with pathologically confirmed Intermediate/High AD from 3 Alzheimer's Disease Research Centers. Regional arteriolosclerosis, cerebral amyloid angiopathy (CAA), cored plaques (CPs), diffuse plaques (DPs), neurofibrillary tangles (NFTs), neuritic plaques (NPs), and neuropil threads (NTs) were semi-quantitatively assessed by adapting established scoring schemes. Differences in neuropathology by cardiovascular risk factor status were assessed using Wilcoxon rank-sum tests and ordinal logistic regression models adjusted for ethnicity, sex, age at death, and center. In adjusted analyses, diabetes was associated with higher frontal NTs (odds ratio, 3.2 [95% CI, 1.2-8.4]). Hypercholesterolemia was associated with higher CAA in the parietal lobe (odds ratio, 2.7 [95% CI, 1.3-5.8]) and posterior hippocampus (odds ratio, 2.8 [95% CI, 1.3-6.1]). None of these associations remained statistically significant following false discovery rate (FDR) correction. These findings suggest vascular risk factors do not substantially modify the burden of AD pathology once advanced disease is present and any independent effects on AD-related lesions are likely modest within this select cohort.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075049","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

CDKN2A/B status can be assessed by p16/MTAP immunohistochemistry as a practical surrogate in pleomorphic xanthoastrocytoma and high-grade astrocytoma with piloid features. CDKN2A/B的状态可以通过p16/MTAP免疫组织化学作为多形性黄色星形细胞瘤和具有核样特征的高级星形细胞瘤的实用替代品来评估。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-23 DOI: 10.1093/jnen/nlag086

Giorgia Antonia Simboli, Audrey Rousseau, Laetitia Basset, Raphaël Saffroy, Lauren Hasty, Farah Sassi, Alice Métais, Pascale Varlet, Arnault Tauziède-Espariat

{"title":"CDKN2A/B status can be assessed by p16/MTAP immunohistochemistry as a practical surrogate in pleomorphic xanthoastrocytoma and high-grade astrocytoma with piloid features.","authors":"Giorgia Antonia Simboli, Audrey Rousseau, Laetitia Basset, Raphaël Saffroy, Lauren Hasty, Farah Sassi, Alice Métais, Pascale Varlet, Arnault Tauziède-Espariat","doi":"10.1093/jnen/nlag086","DOIUrl":"https://doi.org/10.1093/jnen/nlag086","url":null,"abstract":"The presence of a CDKN2A homozygous deletion (HD) plays an important role in the diagnostic approach of neuropathologists to several central nervous system (CNS) tumors. CDKN2A is located on chromosome 9p21, next to CDKN2B and MTAP, and encodes for the protein p16. CDKN2A/B HD constitutes a frequent alteration in some circumscribed gliomas such as high-grade astrocytomas with piloid features (HGAP) and pleomorphic xanthoastrocytomas (PXA). The diagnosis of these tumor types remains complex and having a rapid and easy tool to suggest these diagnoses would be useful. Herein, we studied a cohort of 42 HGAP and PXA to analyze the concordance of CDKN2A/B and MTAP status between 3 different molecular techniques (FISH, DNA-methylation profiling providing copy number variation analysis, and SNP array), and compared the results to those of p16 and MTAP immunohistochemistry. HD was present in 11/12 HGAP and 28/30 PXA, however, with a wide variety of deletion size, including of CDKN2A, CDKN2B, and MTAP genes. There was excellent concordance between p16/MTAP immunoexpression and the genetic detection of HD, demonstrating 100% sensitivity and 100% specificity. In conclusion, combined p16/MTAP IHC presented a positive predictive value for detecting HD and may assist neuropathologists in their diagnostic approach to circumscribed glial/glioneuronal tumors.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030881","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

Epigenetic deregulation in adult gliomas: A key driver of molecular heterogeneity and precision oncology. 成人胶质瘤的表观遗传失调：分子异质性和精确肿瘤学的关键驱动因素。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-19 DOI: 10.1093/jnen/nlag096

Elifcan Gezer, Hamed Charkhian, Seref Bugra Tuncer

{"title":"Epigenetic deregulation in adult gliomas: A key driver of molecular heterogeneity and precision oncology.","authors":"Elifcan Gezer, Hamed Charkhian, Seref Bugra Tuncer","doi":"10.1093/jnen/nlag096","DOIUrl":"https://doi.org/10.1093/jnen/nlag096","url":null,"abstract":"Gliomas, particularly glioblastoma, are characterized by profound molecular and cellular heterogeneity that drives tumor progression, therapeutic resistance, and poor clinical outcomes. Increasing evidence indicates that epigenetic deregulation, extending beyond genetic alterations, plays a central role in glioma initiation, evolution, and treatment response. This review summarizes current advances in the epigenetic landscape of adult gliomas with particular emphasis on the interplay between DNA methylation, histone modifications, chromatin remodeling and their contributions to molecular heterogeneity and precision neuro-oncology. We discuss key epigenetic mechanisms, including global DNA hypomethylation, promoter CpG island hypermethylation, histone acetylation and methylation and their effects on genome stability, transcriptional regulation, stemness, immune modulation, metabolic reprogramming, and therapeutic resistance. Clinically relevant biomarkers, including O6-methylguanine-DNA methyltransferase promoter methylation and the glioma CpG island methylator phenotype, are highlighted alongside emerging therapeutic targets such as histone deacetylases, Enhancer of Zeste Homologue 2, G9a, and protein arginine methyltransferase 5. We further examine the impact of spatial and temporal epigenetic heterogeneity on biomarker interpretation and treatment selection, as well as recent advances in methylation-based tumor classification. Collectively, this review highlights epigenetic deregulation as both a fundamental driver of adult glioma biology and a promising foundation for precision oncology.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008633","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

MyD88 deficiency modestly attenuates disease in a Leigh syndrome mouse model while enrofloxacin accelerates disease. 在Leigh综合征小鼠模型中，MyD88缺乏适度减轻疾病，而恩诺沙星加速疾病。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-16 DOI: 10.1093/jnen/nlag102

Allison R Hanaford, Elizaveta A Olkhova, Ryan Liao, Ashley Ching, Alvin Huang, Erin Shien Hsieh, Kino Watanabe, Yihan Chen, Megan Wichman, Noelle Hwang, Katerina James, Michael Mulholland, Vivian Truong, Holly Coulson, Kerry Gibbins, Owen Cairns, Anastasia Dimitriou, Ernst-Bernhard Kayser, Brittany M Johnson, Sarkar Surojit, Vandana Kalia, Simon C Johnson

{"title":"MyD88 deficiency modestly attenuates disease in a Leigh syndrome mouse model while enrofloxacin accelerates disease.","authors":"Allison R Hanaford, Elizaveta A Olkhova, Ryan Liao, Ashley Ching, Alvin Huang, Erin Shien Hsieh, Kino Watanabe, Yihan Chen, Megan Wichman, Noelle Hwang, Katerina James, Michael Mulholland, Vivian Truong, Holly Coulson, Kerry Gibbins, Owen Cairns, Anastasia Dimitriou, Ernst-Bernhard Kayser, Brittany M Johnson, Sarkar Surojit, Vandana Kalia, Simon C Johnson","doi":"10.1093/jnen/nlag102","DOIUrl":"10.1093/jnen/nlag102","url":null,"abstract":"Primary genetic mitochondrial diseases (GMDs) are clinically and genetically diverse diseases. Leigh syndrome (LS), the most common pediatric presentation of GMD is a severe progressive multi-system disorder with diverse manifestations. No effective treatments currently exist. Recent data from the Ndufs4(-/-) LS mouse model show that peripheral macrophages contribute to brain lesions, that disease is driven by innate immune populations and that depletion of innate immune cells prevents disease. However, the mechanisms underlying the immune activation in LS remain unknown. Certain mitochondrial macromolecules retain bacterial signatures and can act as potent agonists for innate immune pathways. For example, cytoplasmic mitochondrial RNA and DNA are detected by toll-like receptors (TLRs) at the endosome and may mediate innate immune activation in LS. To assess TLR signaling in an LS mouse model, we generated TLR signaling-deficient Ndufs4(-/-)/MyD88(-/-) animals. Prophylactic antibiotic treatment with enrofloxacin enabled production of MyD88(-/-) animals from Ndufs4(+/-)/MyD88(+/-) breeder pairs. Loss of MyD88 in Ndufs4(-/-) animals increased survival and delayed the onset but disease courses were not altered. We conclude that Myd88-mediated immune signaling is not a primary driver of LS. Notably, prophylactic enrofloxacin treatment, which was necessary for production of MyD88(-/-) animals modestly decreased survival and accelerated disease. The impact of enrofloxacin and similar drugs in mitochondrial diseases warrants further investigation.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982841","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 mechanisms of maturation in neurogenic embryonal tumors of peripheral and central localization. 外周和中枢定位的神经源性胚胎肿瘤成熟的分子机制。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-11 DOI: 10.1093/jnen/nlag095

Alexander E Druy, Ivan A Zverev, Natalia A Andreeva, Alexandra V Tarakanova, Maria A Senchenko, Nina V Gegeliya, Margarita A Zaytseva, Agunda V Sanakoeva, Agnesa V Panferova, Ruslan K Abasov, Natalia Y Usman, Vera S Petrova, Dmitry M Konovalov, Grigorii A Raskin, Galina A Novichkova, Nikolay S Grachev, Tatyana V Shamanskaya, Denis Y Kachanov, Ludmila I Papusha

{"title":"Molecular mechanisms of maturation in neurogenic embryonal tumors of peripheral and central localization.","authors":"Alexander E Druy, Ivan A Zverev, Natalia A Andreeva, Alexandra V Tarakanova, Maria A Senchenko, Nina V Gegeliya, Margarita A Zaytseva, Agunda V Sanakoeva, Agnesa V Panferova, Ruslan K Abasov, Natalia Y Usman, Vera S Petrova, Dmitry M Konovalov, Grigorii A Raskin, Galina A Novichkova, Nikolay S Grachev, Tatyana V Shamanskaya, Denis Y Kachanov, Ludmila I Papusha","doi":"10.1093/jnen/nlag095","DOIUrl":"https://doi.org/10.1093/jnen/nlag095","url":null,"abstract":"Tumor maturation is a property of neuroblastomas but can also be observed in unique cases of primary brain malignancies. We hypothesized that the mechanisms of peripheral and central neurogenic tumor maturation could be similar. This study encompassed 19 cases of neuroblastoma and solitary cases of CNS tumors having undergone a morphologically verified maturation. The tumors were analyzed by sequencing and gene expression profiling. We revealed potential similarity of different tumor types upon maturation, associated with stimulated MAPK, PI3K-AKT-mTOR, and TrkA signaling and suppressed regulation of cell cycle and DNA replication and repair. Tumors completing maturation similarly showed enhanced immunogenicity. The levels of NTRK2 expression increased during maturation. Expression of NTRK1 and positive epigenetic regulators (SWI/SNF subunits) increased prior to maturation and decreased upon the differentiation completion. Expression of negative epigenetic regulators EZH2, HDAC10, HDAC2, and DNMT3A decreased in maturing tumors. These data suggest that central and peripheral neurogenic tumors are likely to have common maturation mechanisms. Molecular scenarios associated with neuroblastoma maturation could be: (1) TrkA signaling (seen in cases presenting in < 18-month-olds), or (2) altered expression of epigenetic regulators and transcription factors (seen in cases presenting in >18-month-olds); treatment-induced maturation of CNS malignancies could involve both scenarios.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944877","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

Rapid diagnosis of Fusobacterium nucleatum-associated brain abscess using metagenomic next-generation sequencing: A case series. 使用新一代宏基因组测序快速诊断核梭杆菌相关脑脓肿：一个病例系列。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-04 DOI: 10.1093/jnen/nlag047

Yu Chen, Ai-Seon Kuan, Po-Hsiang Liao, Wei-Hsin Wang, Yen-Chia Chen

引用次数: 0