{"title":"Biological role and clinicopathological significance of leucine-rich α-2 glycoprotein 1 in the glioblastoma microenvironment.","authors":"Takuya Furuta, Hiroaki Miyoshi, Mayuko Moritsubo, Riho Nakajima, Tetsuya Negoto, Hideo Nakamura, Motohiro Morioka, Yasuo Uchida, Sumio Ohtsuki, Mitsutoshi Nakada","doi":"10.1093/jnen/nlaf049","DOIUrl":"https://doi.org/10.1093/jnen/nlaf049","url":null,"abstract":"<p><p>Pseudoprogression, often misinterpreted as glioblastoma progression on MRI, results from treatment-induced inflammation and can resolve without additional intervention. This study investigated the role of leucine-rich α-2 glycoprotein 1 (LRG1) in the glioblastoma microenvironment. Leucine-rich α-2 glycoprotein 1 is associated with inflammation and prognosis in various diseases and its blood concentrations reflect disease-related inflammation. We focused on LRG1 expression in reactive astrocytes and assessed its potential as a biomarker for glioblastoma pseudoprogression. Cases with high LRG1 expression exhibited a distinct molecular profile, with increased angiogenesis-related gene expression and reduced stem cell-related gene activity, underscoring its dual role in tumor biology and progression. In vitro experiments demonstrated that LRG1 suppressed tumor cell invasion, supporting its inverse correlation with tumor cell stemness. Immunohistochemical analysis revealed that astrocytic LRG1 was associated with heightened peritumoral inflammation, characterized by CD8+ T-cell infiltration at the tumor periphery; this correlated with higher pseudoprogression rates and poorer prognosis. By providing a histopathological marker for pseudoprogression, LRG1 complements current imaging modalities and offers a novel approach to addressing unresolved diagnostic challenges in glioblastoma. These findings establish LRG1 as a promising biomarker that could aid clinicians in distinguishing pseudoprogression from true progression, ultimately enhancing personalized treatment strategies for glioblastoma patients.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026613","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}
Mengting Qian, Zheng Wang, Hang Liu, Xinyu Zhang, Jingyi Xu, Yiwen Zhang, Ligang Chen, Zhengjun Zhou, Yang Yu, Wei Dong
{"title":"Reactive astrocytes in spinal cord injury: An analysis of heterogeneity based on temporality and spatiality, potential therapies, and limitations.","authors":"Mengting Qian, Zheng Wang, Hang Liu, Xinyu Zhang, Jingyi Xu, Yiwen Zhang, Ligang Chen, Zhengjun Zhou, Yang Yu, Wei Dong","doi":"10.1093/jnen/nlaf042","DOIUrl":"https://doi.org/10.1093/jnen/nlaf042","url":null,"abstract":"<p><p>Spinal cord injury (SCI) constitutes a profound central nervous system disorder characterized by significant neurological dysfunction and sensory loss below the injury site. SCI elicits a multifaceted cellular response in which the proliferation of reactive astrocytes and the ensuing diversity in their functions and phenotypes play pivotal roles within the injury microenvironment, especially during the secondary phases of the condition. This review explores the activation and heterogeneity of astrocytes following SCI. It underscores the necessity of delineating the heterogeneity among reactive astrocyte subpopulations throughout the secondary injury phase of SCI. Developing therapeutic strategies that capitalize on the beneficial properties of certain reactive astrocyte subpopulations while mitigating the adverse effects of others could have profound implications for future clinical management of SCI.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015325","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}
Joshua E Mayfield, Alexander J Rajic, Patricia Aguilar-Calvo, Katrin Soldau, Samantha Flores, Roger Lawrence, Biwsa Choudhury, Majid Ghassemian, Donald P Pizzo, Steven L Wagner, Garrett A Danque, Paige Sumowski, Lawrence A Hansen, Vanessa Goodwill, Jeffery D Esko, Christina J Sigurdson
{"title":"Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of unsubstituted glucosamine and extracellular proteins.","authors":"Joshua E Mayfield, Alexander J Rajic, Patricia Aguilar-Calvo, Katrin Soldau, Samantha Flores, Roger Lawrence, Biwsa Choudhury, Majid Ghassemian, Donald P Pizzo, Steven L Wagner, Garrett A Danque, Paige Sumowski, Lawrence A Hansen, Vanessa Goodwill, Jeffery D Esko, Christina J Sigurdson","doi":"10.1093/jnen/nlaf018","DOIUrl":"10.1093/jnen/nlaf018","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer's disease in which amyloid-β (Aβ) deposits in cerebral and leptomeningeal vessel walls, predisposing vessels to micro- and macro-hemorrhages. The vessel walls contain distinct proteins and heparan sulfate (HS), yet how vascular proteins and HS jointly associate with Aβ is unknown. We conducted the first multi-omics study to systematically characterize the proteins as well as the HS abundance, sulfation level, and disaccharide composition of leptomeninges from 23 moderate to severe CAA cases and controls. We then analyzed the associations between Aβ and other proteins, HS, and apolipoprotein E genotype. We found an increase in a minor HS disaccharide containing unsubstituted glucosamine, as well as 6-O sulfated disaccharides; Aβ40 levels positively correlated with unsubstituted glucosamine. There was also an increase in extracellular proteins derived from brain parenchyma or plasma, including olfactomedin-like protein 3, fibrinogen, serum amyloid protein, apolipoprotein E, and secreted frizzled related protein-3. Our findings of vascular HS and protein alterations specific to CAA-affected leptomeningeal vessels provide molecular insight into the extracellular remodeling that co-occurs with Aβ deposits and may indicate a basis for antemortem diagnostic assay development and therapeutic strategies to impede Aβ-HS interactions.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"398-411"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743236","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}
Jr-Jiun Liou, Jinghang Li, Jacob Berardinelli, Hecheng Jin, Tales Santini, Jaehoon Noh, Nadim Farhat, Minjie Wu, Howard J Aizenstein, Joseph M Mettenburg, William H Yong, Elizabeth Head, Milos D Ikonomovic, Tamer S Ibrahim, Julia K Kofler
{"title":"Correlating hippocampal and amygdala volumes with neuropathological burden in Down syndrome and Alzheimer's disease and related neurodegenerative pathologies using 7T postmortem MRI.","authors":"Jr-Jiun Liou, Jinghang Li, Jacob Berardinelli, Hecheng Jin, Tales Santini, Jaehoon Noh, Nadim Farhat, Minjie Wu, Howard J Aizenstein, Joseph M Mettenburg, William H Yong, Elizabeth Head, Milos D Ikonomovic, Tamer S Ibrahim, Julia K Kofler","doi":"10.1093/jnen/nlaf010","DOIUrl":"10.1093/jnen/nlaf010","url":null,"abstract":"<p><p>Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), is common in elderly brains and often seen in conjunction with Alzheimer's disease neuropathologic change (ADNC). LATE-NC typically begins in the amygdala and spreads to the hippocampus and neocortex. Whether it contributes to hippocampal and amygdala atrophy in Down syndrome (DS) remains unexplored. We analyzed amygdala and hippocampal volumes and neuropathological burden in 12 DS cases and 54 non-DS cases with AD and related neurodegenerative pathologies (ADRNP) using 7 Tesla (7T) postmortem ex vivo MRI. Postmortem and antemortem hippocampal volumes were significantly correlated in a subset of 17 cases with available antemortem MRI scans. DS cases had smaller hippocampal and amygdala volumes than ADRNP cases; these correlated with more severe Braak stage but not with Thal phase. LATE-NC and hippocampal sclerosis (HS) were uncommon in DS cases. In ADRNP cases, lower hippocampal volumes associated with dementia duration, advanced Thal phase, Braak NFT stage, C score, LATE-NC stage, HS and arteriolosclerosis severity; reduced amygdala volumes correlated with severe LATE-NC stage, HS, and arteriolosclerosis severity, but not with Thal phase or Braak NFT stage. Lewy body pathology did not affect hippocampal or amygdala volume in either cohort. Thus, hippocampal volumes in ADRNP were influenced by both ADNC and LATE-NC, and amygdala volumes were primarily influenced by LATE-NC. In DS, hippocampal and amygdala volumes were primarily influenced by tau pathology.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"364-378"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597038","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}
Shannon M Robins, Mary Rosenblatt, Jeffrey N Bruce, Peter Canoll, George Zanazzi
{"title":"Solitary fibrous tumor in the pineal region: A series of 5 cases and literature review.","authors":"Shannon M Robins, Mary Rosenblatt, Jeffrey N Bruce, Peter Canoll, George Zanazzi","doi":"10.1093/jnen/nlaf008","DOIUrl":"10.1093/jnen/nlaf008","url":null,"abstract":"<p><p>Solitary fibrous tumors (SFTs) are fibroblastic mesenchymal neoplasms defined by the presence of a NAB2::STAT6 fusion and exhibit a broad range of behaviors. SFTs in the pineal region are poorly understood due to the limited number of reported cases. Here, we report a 48-year-old woman with a pineal region SFT who subsequently developed metastatic left para-falcine parieto-occipital and right lung upper lobe SFTs over the next 12 years. This was the only pineal SFT identified in an institutional cohort of 34 resected pineal region lesions. Review of another, much larger institutional cohort of pineal region lesions revealed 4 additional patients with SFT but none with extracranial metastasis. We present descriptions of their clinical presentations, treatments, histopathologic findings, available genomic alterations, and longitudinal outcomes. Finally, we performed a comprehensive literature search and identified 19 individual patients with pineal region SFTs. None of these reported neoplasms had an extracranial metastasis. Taken together, this work contributes to the growing body of data characterizing this rare tumor with aggressive potential and reinforces SFTs as a possible differential diagnosis for pineal region tumors.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"379-390"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414613","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}
{"title":"Re: Article by Machaalani et al. concerning dentate gyrus dysplasia.","authors":"Douglas C Miller","doi":"10.1093/jnen/nlaf011","DOIUrl":"10.1093/jnen/nlaf011","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"444"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557188","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}
Karsten Ruscher, Georgios Michalettos, Sami Abu Hamdeh, Fredrik Clausen, Amber L Nolan, Johanna Flygt, Ilknur Özen, Niklas Marklund
{"title":"Persistent increase of Nogo-A-positive cells and dynamic reduction in oligodendroglia lineage cells in white matter regions following experimental and clinical traumatic brain injury.","authors":"Karsten Ruscher, Georgios Michalettos, Sami Abu Hamdeh, Fredrik Clausen, Amber L Nolan, Johanna Flygt, Ilknur Özen, Niklas Marklund","doi":"10.1093/jnen/nlaf017","DOIUrl":"10.1093/jnen/nlaf017","url":null,"abstract":"<p><p>White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A+ cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A+ cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid percussion injury (cFPI) in mice. In addition, the number of Olig2+ cells in the CC and capsula externa remained constant, while the numbers of Olig2+/CC1+ and GST-π+ mature oligodendrocytes declined throughout the observation time of 18 months. A significantly lower number of Olig2+/CC1+ cells was found in cFPI mice compared to controls at 18 mpi. Persistent vulnerability of oligodendrocytes in combination with dynamic alterations of Nogo-A expression may have implications for the WM atrophy and insufficient recovery observed after TBI.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"423-435"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623408","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}
Julieann C Lee, Amar Gajjar, Melissa R Perrino, Angela Delaney, Christopher L Tinkle, Paul Klimo, Larissa V Furtado, Yen-Chun Liu, Alex Breuer, Soniya N Pinto, Asim K Bag, David W Ellison, Brent A Orr
{"title":"Concurrent Pit-1 and SALL4 staining in primitive component of pituitary blastoma: A case report with clinicopathologic features including Cushing syndrome presentation, germline DICER1 mutation, and significant therapeutic response to chemoradiation.","authors":"Julieann C Lee, Amar Gajjar, Melissa R Perrino, Angela Delaney, Christopher L Tinkle, Paul Klimo, Larissa V Furtado, Yen-Chun Liu, Alex Breuer, Soniya N Pinto, Asim K Bag, David W Ellison, Brent A Orr","doi":"10.1093/jnen/nlae126","DOIUrl":"10.1093/jnen/nlae126","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"436-440"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829012","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}
{"title":"Maximum contrast projection: A powerful tool for biomedical image stack analysis.","authors":"Nat Adamian, Christopher Guirguis, Ansel Link, Nate Jowett, Iván Coto Hernández","doi":"10.1093/jnen/nlaf013","DOIUrl":"10.1093/jnen/nlaf013","url":null,"abstract":"<p><p>Maximum intensity projection is a simple post-hoc dimension reduction approach that yields sharp 2-dimensional images from image stacks but is limited by low signal or high background. Herein, we demonstrated improvement in image contrast using maximum contrast versus maximum intensity projection in 3-dimensional phase-contrast and quantitative phase imaging of frozen cross-sections of murine peripheral nerve. Fresh frozen murine sciatic nerve sections were imaged using 3-dimensional fluorescence, phase-contrast, and quantitative phase microscopy. Images were processed using maximum intensity and maximum contrast projection. Higher image contrast of nerve morphology was obtained when the images were processed with maximum contrast projection. Enhanced image contrast in quantitative phase imaging facilitated label-free multicolor imaging of murine peripheral nerves. Herein, we demonstrate the utility of maximum contrast projection in enhancing image contrast over intensity projection approaches in fluorescence phase-contrast and quantitative phase imaging of nerve histological samples. A user-friendly, open-source Python-based maximum contrast projection algorithm to facilitate the adoption of this technique is provided.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"391-397"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557165","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}