Journal of Neuropathology and Experimental Neurology最新文献

Entorhinal cortex astrocytes in early Alzheimer disease: Human evidence, cross-species circuit rationale, and translational boundaries. 早期阿尔茨海默病的内嗅皮层星形胶质细胞：人类证据、跨物种回路原理和翻译边界。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-05 DOI: 10.1093/jnen/nlag098

Fengjuan Wu, Manxia Wang

{"title":"Entorhinal cortex astrocytes in early Alzheimer disease: Human evidence, cross-species circuit rationale, and translational boundaries.","authors":"Fengjuan Wu, Manxia Wang","doi":"10.1093/jnen/nlag098","DOIUrl":"https://doi.org/10.1093/jnen/nlag098","url":null,"abstract":"Alzheimer disease (AD) pathology affects the transentorhinal/entorhinal region early but whether entorhinal cortex (EC) astrocytes are causal drivers or therapeutic targets remains unresolved. This narrative review evaluates EC astrocytes through an explicit evidence hierarchy. We distinguish: (1) human EC-specific neuropathology, imaging, and transcriptomic findings, (2) human AD astrocyte data lacking EC-cell resolution, (3) mechanistic evidence from animal and cellular models, and (4) translational hypotheses. Human data support early EC vulnerability and region- and stage-dependent astrocyte remodeling, whereas the most direct functional evidence comes from rodent medial EC layer II and should be interpreted as circuit plausibility rather than anatomical equivalence to the human EC. We therefore prioritize candidate astrocyte modules according to astrocyte specificity, relevance to EC or medial temporal pathology, mechanistic links to circuit dysfunction, and the availability of measurable target-engagement readouts. These modules include inflammatory-complement signaling, EAAT2/GLT-1-mediated glutamate clearance, MAO-B/GABA metabolism, AQP4-related gliovascular regulation, astrocytic calcium signaling, and APOE-related lipid handling. Cell transplantation, glial reprogramming, and engineered extracellular vesicles remain experimental platforms. EC astrocytes should therefore be viewed as candidate circuit-glial vulnerability nodes requiring human validation, not as established clinical targets.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897402","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

Correction to: Digital pathology in tau research: A comparison of QuPath and HALO. 修正：tau研究中的数字病理学：QuPath和HALO的比较。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-03 DOI: 10.1093/jnen/nlag064

引用次数: 0

Glioblastoma with ependymal-like features harboring novel CTDSP2::GLI1 and INHBE::GLI1 fusions. 具有室管膜样特征的胶质母细胞瘤含有新的CTDSP2::GLI1和INHBE::GLI1融合体。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-02 DOI: 10.1093/jnen/nlag073

Tristan Mackey, Stephanie Salovesh, Andrew J Tsung, Alexis Carter, Jack Mordeson, Purvi Patel

引用次数: 0

Persistent ultrastructural changes to callosal axons three months after repetitive brain injury across age groups. 重复脑损伤后3个月胼胝体轴突的持续超微结构变化。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-09-01 DOI: 10.1093/jnen/nlag092

Camila Ortiz, Igor Kraev, Radka Gromnicova, Andrew Pearson, Amanda Naaman, Michael Mullan, Fiona Crawford, Joseph Ojo

{"title":"Persistent ultrastructural changes to callosal axons three months after repetitive brain injury across age groups.","authors":"Camila Ortiz, Igor Kraev, Radka Gromnicova, Andrew Pearson, Amanda Naaman, Michael Mullan, Fiona Crawford, Joseph Ojo","doi":"10.1093/jnen/nlag092","DOIUrl":"https://doi.org/10.1093/jnen/nlag092","url":null,"abstract":"Repetitive mild traumatic brain injury (r-mTBI) is strongly associated with the increased risk of developing neurodegenerative diseases. Previously, we have revealed the histopathological, biochemical, and transcriptional changes following exposure to chronic r-mTBI in wild-type (WT) mice. Herein, we performed a complementary electron microscopy analysis in a young adult (3-month-old) WT cohort to reveal the ultrastructural changes observed 3 months following chronic r-mTBI. Additionally, because age at injury has been associated with an increased risk for poorer outcomes after TBI, an older WT cohort (12-month-old, middle-aged) was included to determine this relationship. While the cortical grey-matter exhibited minimal ultrastructural abnormalities after r-mTBI, we observed prominent TBI-related changes in the corpus callosum, including increased axonal g-ratios and higher density of degenerating axons in both cohorts. However, no age-dependent injury differences were observed across measured parameters, except for a notable TBI-dependent increase in phagolysosome-bearing perivascular cells within the corpus callosum of injured aged mice compared to younger TBI counterparts. Collectively, these findings suggest that chronic r-mTBI in young adulthood and middle age produces similar white matter ultrastructural changes 3 months after r-mTBI. Future studies are warranted to determine whether ultrastructural differences emerge with injuries administered earlier in life or at advanced age.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874478","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

Infection with Western equine encephalitis virus causes severe regional glial reactivity and neurodegeneration in the hippocampus with progressive accumulation of amyloid-β. 西部马脑炎病毒感染导致海马严重的区域胶质反应性和神经变性，伴有淀粉样蛋白-β的进行性积累。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-08-28 DOI: 10.1093/jnen/nlag097

Aidan M Briggs, Adam J Schuller, Megan R Hager, Omar A Yanouri, Savannah M Rocha, Collin M Bantle, Debotri Chatterjee, Richard J Smeyne, Ronald B Tjalkens

{"title":"Infection with Western equine encephalitis virus causes severe regional glial reactivity and neurodegeneration in the hippocampus with progressive accumulation of amyloid-β.","authors":"Aidan M Briggs, Adam J Schuller, Megan R Hager, Omar A Yanouri, Savannah M Rocha, Collin M Bantle, Debotri Chatterjee, Richard J Smeyne, Ronald B Tjalkens","doi":"10.1093/jnen/nlag097","DOIUrl":"https://doi.org/10.1093/jnen/nlag097","url":null,"abstract":"Encephalitic alphaviruses such as Western equine encephalitis virus (WEEV) result in significant morbidity through acute viremia and postencephalitic neurologic dysfunction. Viral neurotropism is linked to chronic glial-mediated neuroinflammation and increased risk for neurodegenerative disorders including Alzheimer disease and Parkinson disease. We previously showed that sublethal WEEV infection induces nigrostriatal gliosis, neuronal loss, and Parkinsonian-like motor deficits in mice. However, the temporal progression of glial activation and neurodegeneration in brain regions relevant to dementia remains unclear. To address this, we performed a longitudinal assessment of hippocampal pathology following intranasal infection with McMillan WEEV. Brain tissue was collected at 1, 2, and 4 weeks postinfection and analyzed using high-content fluorescence imaging, deep learning-based image analysis, and population-level cellular phenotyping. We observed a marked increase in gliosis peaking at 1-week postinfection, coinciding with fibrotic, immune cell-dense lesions that inversely correlated with eosinophilic neuronal density. Automated skeletonization analysis revealed increased astrocyte reactivity and a predominantly bushy microglial morphology at this time point. Heat map densitometry further demonstrated progressive amyloid-β accumulation across all time points. Together, these findings define a dynamic sequence of glial activation, lesion formation, and protein aggregation underlying WEEV-induced hippocampal neurotoxicity.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850725","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

Comparison of quantitative digital and semiquantitative assessments of tau pathology in relation to regional in vivo tau PET. 局部体内tau PET病理定量数字和半定量评估的比较。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-08-27 DOI: 10.1093/jnen/nlag093

Cecilia Tremblay, Tove Freiburghaus, Daria Pawlik, Kevin Oliveira Hauer, Geidy E Serrano, Yashar Zeighami, Mahsa Dadar, Anthony J Intorcia, Rik Ossenkoppele, Michael J Pontecorvo, Oskar Hansson, Ruben Smith, Thomas G Beach

{"title":"Comparison of quantitative digital and semiquantitative assessments of tau pathology in relation to regional in vivo tau PET.","authors":"Cecilia Tremblay, Tove Freiburghaus, Daria Pawlik, Kevin Oliveira Hauer, Geidy E Serrano, Yashar Zeighami, Mahsa Dadar, Anthony J Intorcia, Rik Ossenkoppele, Michael J Pontecorvo, Oskar Hansson, Ruben Smith, Thomas G Beach","doi":"10.1093/jnen/nlag093","DOIUrl":"https://doi.org/10.1093/jnen/nlag093","url":null,"abstract":"Quantitative digital image analysis has emerged as a powerful tool for assessing neuropathological burden. Although previous studies have compared quantitative digital and semiquantitative pathology measures, their respective relationships with regionally corresponding in vivo tau PET measures remain poorly characterized. We compared quantitative digital pathology quantification and semiquantitative regional gradings of phosphorylated tau (ptau) immunohistochemical staining and assessed their correlations with regional in vivo [18F]flortaucipir standardized uptake value ratios (SUVRs) in 52 cases from the AVID A16 end-of-life study. Digital pathology quantification and semiquantitative gradings of ptau were strongly correlated across all 19 cortical and mesial temporal regions examined (Spearman's rho range: 0.6-0.9; all P < .0001). Both approaches showed similarly robust associations with regionally corresponding tau PET SUVRs. Direct comparison of matched correlation coefficients revealed stronger PET-pathology associations for the digital quantification in the left amygdala and the inferior parietal lobule. Overall, digital pathology quantification and semiquantitative assessments of ptau pathology yielded highly comparable results, both in the quantification of regional pathology burden and in their relationships with tau PET measures. These findings support the use of digital pathology quantification methods and suggest that semiquantitative pathology gradings remain a valid and informative approach for clinicopathological correlation studies.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840520","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

Clinicopathologic features of spinal arachnoiditis in patients with surgically treated syringomyelia: A retrospective study of 60 cases. 60例脊髓空洞术后脊髓蛛网膜炎的临床病理特征分析。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-08-27 DOI: 10.1093/jnen/nlag094

Joseph Y Choi, Shantelle A Graff, Hasita V Nalluri, Martha M Quezado, Pinar E Zerk, Dragan Maric, Dorian B McGavern, John D Heiss

{"title":"Clinicopathologic features of spinal arachnoiditis in patients with surgically treated syringomyelia: A retrospective study of 60 cases.","authors":"Joseph Y Choi, Shantelle A Graff, Hasita V Nalluri, Martha M Quezado, Pinar E Zerk, Dragan Maric, Dorian B McGavern, John D Heiss","doi":"10.1093/jnen/nlag094","DOIUrl":"https://doi.org/10.1093/jnen/nlag094","url":null,"abstract":"Arachnoiditis develops from inflammatory processes in the intrathecal space and can cause syringomyelia, myelopathy, radiculopathy, and chronic pain. Understanding inflammatory and fibrotic mechanisms may identify therapeutic targets. We performed a retrospective study of 60 adults who had undergone surgery for arachnoiditis-associated syringomyelia. Clinical status was assessed preoperatively and at 3 to 4 months post-surgery. Cerebrospinal fluid (CSF) was obtained preoperatively, 1-week post-operatively, and at 3 to 4 months. Operative arachnoid adhesion specimens underwent histopathologic review and immunofluorescence staining with quantitative assessment of fibrosis, inflammation, and human endogenous retrovirus group K (HERV-K) antigens. Lesions had mid-thoracic predominance and heterogeneous etiologies. Median CSF white cell counts were low preoperatively (1 cell/µL, range: 0 to 11 cells/µL). Tissue profiling supported a fibroblast-associated, scar-forming lesion (mean density of CRABP2 = 434 cells/mm2, ER-TR7 = 430 cells/mm2) with moderate collagen I deposition (8.1% of specimens), less adaptive immune signals (9 to 180 cells/mm2), and minimal HERV-K staining (1.1% of tissue). In arachnoiditis-associated syringomyelia, preoperative CSF had few white blood cells; 1-week postoperative CSF had RBC and WBC counts consistent with postoperative meningeal irritation. Chronic fibrosis characterized arachnoid tissue removed at surgery. Histology and immunohistochemical staining suggested that arachnoiditis manifested as a fibroproliferative, adhesive phenotype within the subarachnoid space.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840477","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

Cushing disease caused by a TBX19/PIT1 co-expressing pituitary adenoma/pituitary neuroendocrine tumor. TBX19/PIT1共表达垂体腺瘤/垂体神经内分泌肿瘤所致的库欣病。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-08-27 DOI: 10.1093/jnen/nlag084

Christie G Turin, Angus M S Toland, Margaret E Wierman, Kevin O Lillehei, B K Kleinschmidt-DeMasters

引用次数: 0

An open-source application for automated quantification of Ki-67 proliferative index in meningiomas. 用于脑膜瘤Ki-67增殖指数自动定量的开源应用程序。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-08-21 DOI: 10.1093/jnen/nlag083

Aaishah R Raquib, Steven N Schwartz, Shan H Siddiqi, Hemant Varma

{"title":"An open-source application for automated quantification of Ki-67 proliferative index in meningiomas.","authors":"Aaishah R Raquib, Steven N Schwartz, Shan H Siddiqi, Hemant Varma","doi":"10.1093/jnen/nlag083","DOIUrl":"https://doi.org/10.1093/jnen/nlag083","url":null,"abstract":"Ki-67 is a proliferative biomarker used for diagnosis, grading, and prognosis of various cancer types. This involves manually counting up to 1000 cells, a laborious and error-prone process due to interobserver variability. We developed and validated an open access automated tool for quantification of Ki-67-positive cells in meningiomas, the most common primary brain tumor. The automated counting algorithm was trained using immunohistochemical Ki-67-stained sections from 10 meningioma samples and tested on another 50 meningioma samples. Automated counts were compared to manual counts from 2 independent observers using intraclass correlations (ICC) and Pearson correlation. The 2 observers yielded similar counts across all 50 slides (ICC = 0.802, Pearson r = 0.77). The automated count showed significantly greater correlation with both manual counts (ICC = 0.94, P = 2.5×10-5; ICC = 0.90, P = 0.011). The Pearson correlation between the automated count and both manual counts (r = 0.89 in both cases) was significantly stronger than the correlation between the 2 manual counts (P < 10-6 in each case). Thus, the automated Ki-67 count predicted both manual counts better than manual counts predicted each other. The algorithm is freely available as a web application (https://Ki67.app) and as open-source code (https://github.com/aaishahraquib/Ki67-counter). This freely available counter will provide a user-friendly, time efficient, and accurate resource for practicing pathologists.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794608","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