Brain Pathology最新文献

Dysregulation of the endosomal sorting complex III is linked to neurodegeneration in progressive multiple sclerosis. 内体分选复合体III的失调与进行性多发性硬化症的神经变性有关。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-07-24 DOI: 10.1111/bpa.70034

Carmen Picon, Robertas Aleksynas, Marcelina Wojewska, Francesco de Virgiliis, Doron Merkler, Richard Reynolds

{"title":"Dysregulation of the endosomal sorting complex III is linked to neurodegeneration in progressive multiple sclerosis.","authors":"Carmen Picon, Robertas Aleksynas, Marcelina Wojewska, Francesco de Virgiliis, Doron Merkler, Richard Reynolds","doi":"10.1111/bpa.70034","DOIUrl":"https://doi.org/10.1111/bpa.70034","url":null,"abstract":"Multiple sclerosis (MS) is a chronic neuroinflammatory disease that progresses to a stage marked by irreversible neurological decline and widespread neurodegeneration. Necroptosis, a regulated form of cell death primarily triggered by tumor necrosis factor (TNF), has been implicated in neuronal loss in progressive MS. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery, essential for plasma membrane repair and vesicle trafficking, is known to counteract necroptosis in non-neural cells. In this study, we investigated whether ESCRT dysfunction contributes to neurodegeneration in the MS cortex. We identified a significant dysregulation of ESCRT-III complex components, particularly VPS4B and CHMP2A, in neurons of MS cortical grey matter. This dysregulation correlated with reduced neuronal density and increased meningeal inflammation. Notably, both demyelinated and normal-appearing grey matter showed decreased VPS4B, while CHMP2A loss was more restricted to areas of demyelination. These findings suggest that impaired ESCRT-III function may increase neuronal vulnerability to necroptosis and contribute to disease progression in MS. Our results highlight a novel pathway linking neuroinflammation, ESCRT dysfunction, and neuronal death, with potential therapeutic implications for neuroprotection in progressive MS.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70034"},"PeriodicalIF":5.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706408","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}

引用次数: 0

Dendritic location of dystrophic neurites in FTLD-TDP type C with annexinopathy. 伴有膜联病的FTLD-TDP C型患者营养不良神经突的树突位置。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-07-23 DOI: 10.1111/bpa.70032

Allegra Kawles, Antonia Zouridakis, Caroline Nelson, Rachel Keszycki, Grace Minogue, Alyssa Macomber, Pouya Jamshidi, Rudolph J Castellani, Changiz Geula, Tamar Gefen, M-Marsel Mesulam

{"title":"Dendritic location of dystrophic neurites in FTLD-TDP type C with annexinopathy.","authors":"Allegra Kawles, Antonia Zouridakis, Caroline Nelson, Rachel Keszycki, Grace Minogue, Alyssa Macomber, Pouya Jamshidi, Rudolph J Castellani, Changiz Geula, Tamar Gefen, M-Marsel Mesulam","doi":"10.1111/bpa.70032","DOIUrl":"https://doi.org/10.1111/bpa.70032","url":null,"abstract":"The type C variant (TDP-C) of FTLD-TDP exhibits unique features, not shared by types A and B, namely the invariable and frequently asymmetric predilection for the anterior temporal lobes (ATL). Depending on the direction of hemispheric asymmetry, the associated clinical features include word comprehension impairment, associative agnosia, and behavioral abnormalities. Current research on TDP-C aims to explore the factors that underlie the selective targeting of the ATL and, more specifically, the cellular details that undermine the behavioral and cognitive functions of this region. Abnormal TDP-C neurites have recently been shown to represent heterodimers with annexin A11 (ANXA11). This feature, not shared by TDP-A or -B, may explain the unique predilection of TDP-C for the ATL. To further explore the subcellular distribution of the pathology, paraffin-embedded sections were stained using fluorescent antibodies for the dendritic marker MAP2 and phosphorylated TDP-43 (pTDP) or ANXA11. Results indicated that approximately half of pTDP/ANXA11 neurites co-localized with MAP2. The actual overlap during life may be much higher but decreased at autopsy through dendritic loss due to prolonged neurodegeneration. The potentially selective and progressive dendritic pathology of TDP-C, quite unique among neurodegenerative entities, may underlie the distinctive perturbation of cortical integrative computations.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70032"},"PeriodicalIF":5.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697701","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}

引用次数: 0

Intraventricular mass in a 49-year-old male. 脑室内肿块，49岁男性。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-07-03 DOI: 10.1111/bpa.70030

Connor R Zuraski, Donald P Pizzo, Jessica D Schulte, Vanessa S Goodwill

引用次数: 0

Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort. 使用数字病理学和深度学习的儿童脑肿瘤分类：在瑞典多中心队列中评估SOTA方法。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-30 DOI: 10.1111/bpa.70029

Iulian Emil Tampu, Per Nyman, Christoforos Spyretos, Ida Blystad, Alia Shamikh, Gabriela Prochazka, Teresita Díaz de Ståhl, Johanna Sandgren, Peter Lundberg, Neda Haj-Hosseini

{"title":"Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort.","authors":"Iulian Emil Tampu, Per Nyman, Christoforos Spyretos, Ida Blystad, Alia Shamikh, Gabriela Prochazka, Teresita Díaz de Ståhl, Johanna Sandgren, Peter Lundberg, Neda Haj-Hosseini","doi":"10.1111/bpa.70029","DOIUrl":"https://doi.org/10.1111/bpa.70029","url":null,"abstract":"Brain tumors are the most common solid tumors in children and young adults, but the scarcity of large histopathology datasets has limited the application of computational pathology in this group. This study implements two weakly supervised multiple-instance learning (MIL) approaches on patch features obtained from state-of-the-art histology-specific foundation models to classify pediatric brain tumors in hematoxylin and eosin whole slide images (WSIs) from a multi-center Swedish cohort. WSIs from 540 subjects (age 8.5 ± 4.9 years) diagnosed with brain tumors were gathered from the six Swedish university hospitals. Instance (patch)-level features were obtained from WSIs using three pre-trained feature extractors: ResNet50, UNI, and CONCH. Instances were aggregated using attention-based MIL (ABMIL) or clustering-constrained attention MIL (CLAM) for patient-level classification. Models were evaluated on three classification tasks based on the hierarchical classification of pediatric brain tumors: tumor category, family, and type. Model generalization was assessed by training on data from two of the centers and testing on data from four other centers. Model interpretability was evaluated through attention mapping. The highest classification performance was achieved using UNI features and ABMIL aggregation, with Matthew's correlation coefficient of 0.76 ± 0.04, 0.63 ± 0.04, and 0.60 ± 0.05 for tumor category, family, and type classification, respectively. When evaluating generalization, models utilizing UNI and CONCH features outperformed those using ResNet50. However, the drop in performance from the in-site to out-of-site testing was similar across feature extractors. These results show the potential of state-of-the-art computational pathology methods in diagnosing pediatric brain tumors at different hierarchical levels with fair generalizability on a multi-center national dataset.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70029"},"PeriodicalIF":5.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526500","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}

引用次数: 0

Multi-pronged analysis of pediatric low-grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with BRAF alterations. 对儿童低级别胶质瘤和神经节胶质瘤的多管齐下分析揭示了与BRAF改变相关的独特肿瘤微环境。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-30 DOI: 10.1111/bpa.70023

Shadi Zahedi, Kent Riemondy, Tian Liu, Andrea M Griesinger, Andrew M Donson, April A Apfelbaum, Rui Fu, Julian Grandvallet Contreras, Michele Crespo, John DeSisto, Madeline M Groat, Emil Bratbak, Adam Green, Todd C Hankinson, Michael Handler, Rajeev Vibhakar, Nicholas Willard, Nicholas K Foreman, Tzu Phang, Jean Mulcahy Levy

{"title":"Multi-pronged analysis of pediatric low-grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with BRAF alterations.","authors":"Shadi Zahedi, Kent Riemondy, Tian Liu, Andrea M Griesinger, Andrew M Donson, April A Apfelbaum, Rui Fu, Julian Grandvallet Contreras, Michele Crespo, John DeSisto, Madeline M Groat, Emil Bratbak, Adam Green, Todd C Hankinson, Michael Handler, Rajeev Vibhakar, Nicholas Willard, Nicholas K Foreman, Tzu Phang, Jean Mulcahy Levy","doi":"10.1111/bpa.70023","DOIUrl":"10.1111/bpa.70023","url":null,"abstract":"Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies. We utilized single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and cytokine analyses to characterize and understand tumor and immune cell heterogeneity of pilocytic astrocytoma (PA) and ganglioglioma (GG). scRNA-seq revealed tumor and immune cells within the tumor microenvironment (TME). Tumor cell subsets include both progenitor and mature cell populations. Immune cells included myeloid and lymphocytic cells. There was a significant difference between the prevalence of two major myeloid subclusters between PA and GG. Bulk and single-cell cytokine analyses evaluated the immune cell signaling cascade with distinct immune phenotypes among tumor samples. KIAA1549-BRAF tumors appeared more immunogenic, secreting higher levels of immune cell activators and chemokines, compared to BRAF V600E tumors. Spatial transcriptomics revealed the differential gene expression of these chemokines and their location within the TME. A multi-pronged analysis demonstrated the complexity of the PA and GG TME and differences between genetic drivers that may influence their response to immunotherapy. Further investigation of immune cell infiltration and tumor-immune interactions is warranted.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70023"},"PeriodicalIF":5.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526499","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}

引用次数: 0

A posterior fossa mass in a 4-year-old female. 一名四岁女性后颅窝肿块。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-24 DOI: 10.1111/bpa.70028

Vy Huynh, M Adelita Vizcaino, Jonathan D Schwartz, J Zachary Wilson, David J Daniels, Julie B Guerin, Benjamin R Kipp, Brent A Orr, Kenneth Aldape, Yi Zhu

引用次数: 0

A young man with multifocal brainstem leptomeningeal disease. 年轻男性多灶性脑干脑脊膜病。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-22 DOI: 10.1111/bpa.70026

Burana Khiankaew, Pornphan Sae-Sim, Pichet Termsarasab, Oranan Tritanon, Theeraphol Panyaping, Paisarn Boonsakan, Vichan Peonim, Virawudh Soontornniyomkij

引用次数: 0

Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy. 小脑缺陷是脊髓性肌萎缩小鼠模型的主要病理。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-21 DOI: 10.1111/bpa.70025

Nicholas C Cottam, Morgan Dowling, Lingling Kong, Michelle Harran Chan-Cortés, Christine J Charvet, Naika Norzeron, Cameron Grover, Melissa A Harrington, Charlotte J Sumner, Jianli Sun

{"title":"Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.","authors":"Nicholas C Cottam, Morgan Dowling, Lingling Kong, Michelle Harran Chan-Cortés, Christine J Charvet, Naika Norzeron, Cameron Grover, Melissa A Harrington, Charlotte J Sumner, Jianli Sun","doi":"10.1111/bpa.70025","DOIUrl":"10.1111/bpa.70025","url":null,"abstract":"Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality worldwide, is caused by reduced levels of the ubiquitous survival motor neuron (SMN) protein in SMA patients. Despite significant advancement in recent research and clinical treatments, the cellular pathologies that underlie SMA disease manifestations are not well characterized beyond those of spinal motor neurons (MNs). We previously reported cerebellar abnormalities in an SMA mouse model at the late stage of the disease, including volumetric deficits and lobule-selective structural changes with Purkinje cell degeneration, with colocalized astrocytic reactivity. However, when these cerebellar defects arise and whether they are a consequence of MN degeneration remain unknown. We used magnetic resonance imaging, immunohistochemistry, and electrophysiology to characterize cerebellar pathology in early-stage symptomatic SMNΔ7 mice and late-stage SMA mice with transgenic rescue of SMN in MNs. We found disproportionate structural and lobule-specific surface area deficits, as well as abnormal functional properties in the cerebella of early symptomatic SMA mice, suggesting that cerebellar pathologies may be a primary contributor to murine SMA phenotypes. Moreover, cerebellar pathologies were not ameliorated in SMA mice with MN rescue, suggesting that cerebellar neurons are independently vulnerable to reduced SMN expression. Overall, our study shows that cerebellar defects are a primary pathology in SMA mouse models and that therapies targeting cerebellar neurons in SMA patients may be needed for optimal treatment outcomes.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70025"},"PeriodicalIF":5.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339901","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}

引用次数: 0

Integration of omics data in the diagnosis and therapy of glioblastoma. 组学数据在胶质母细胞瘤诊断和治疗中的整合。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-17 DOI: 10.1111/bpa.70027

Constantin Möller, Melanie Schoof, Keith L Ligon, Ulrich Schüller

{"title":"Integration of omics data in the diagnosis and therapy of glioblastoma.","authors":"Constantin Möller, Melanie Schoof, Keith L Ligon, Ulrich Schüller","doi":"10.1111/bpa.70027","DOIUrl":"https://doi.org/10.1111/bpa.70027","url":null,"abstract":"Since the 2016 update of the WHO Classification of Tumors of the Central Nervous System, omics data have been officially integrated into the diagnostic process for glioblastoma, the most prevalent and aggressive primary malignant brain tumor in adults. This review will examine the current and future integration of omics data in both the diagnosis and therapy of glioblastomas. The current clinical use of omics data primarily focuses on genomics for determining the IDH- and H3-wildtype status of the tumor, and on epigenomics, such as assessing MGMT promoter methylation status as a prognostic and predictive biomarker. However, it can be anticipated that the usage and importance of omics data will likely increase in the future. This work highlights how omics technologies have significantly enhanced our understanding of glioblastoma, particularly of its extensive heterogeneity. This enhanced understanding has not only improved diagnostic accuracy but has also facilitated the identification of new predictive and/or prognostic biomarkers. It is likely that the ongoing integration of omics data will transform many aspects of the diagnostic process, including sample acquisition. Additionally, omics data will be integrated into future glioblastoma treatment procedures, with possible applications ranging from identifying potential therapeutic targets to selecting individual treatment plans. The implications of the ongoing integration of omics data for clinical routine, future classification systems, and trial design are also discussed in this review, outlining the pivotal role omics data play in shaping future glioblastoma diagnosis and treatment.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70027"},"PeriodicalIF":5.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315947","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}

引用次数: 0

Contribution of α-synuclein cytopathologies to distinct seeding of misfolded α-synuclein. α-突触核蛋白细胞病理学对α-突触核蛋白错误折叠的不同播种的贡献。

IF 5.8 2区医学

Brain Pathology Pub Date : 2025-06-16 DOI: 10.1111/bpa.70024

Ain Kim, Ivan Martinez-Valbuena, Krisztina Danics, Shelley L Forrest, Gabor G Kovacs

{"title":"Contribution of α-synuclein cytopathologies to distinct seeding of misfolded α-synuclein.","authors":"Ain Kim, Ivan Martinez-Valbuena, Krisztina Danics, Shelley L Forrest, Gabor G Kovacs","doi":"10.1111/bpa.70024","DOIUrl":"https://doi.org/10.1111/bpa.70024","url":null,"abstract":"Synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of misfolded α-synuclein (αSyn), predominantly in oligodendrocytes in multiple system atrophy (MSA) and in neurons in Lewy body diseases (LBD). The contribution of αSyn cytopathologies to the pathogenesis of these diseases is underappreciated. Seed amplification assays of MSA and LBD brains have revealed striking differences in αSyn seeding between regions and cases. Therefore, our aim was to evaluate whether different brain regions containing distinct αSyn cytopathologies contribute to different seeding characteristics. We collected 2-mm micro-punches of regions in MSA (n = 10) and LBD (n = 15) cases from formalin-fixed paraffin-embedded tissues. We performed double immuno-labeling for disease-associated αSyn and cellular markers on tissue microarrays, evaluated co-deposition of other neurodegenerative disease-related proteins and, from the same micro-punched samples, we analyzed αSyn seeding. Based on these variables, machine learning algorithms were used to reduce dimensionality of the dataset and cluster the regions in MSA and LBD cases, revealing that different compositions of αSyn cytopathologies influence αSyn seeding patterns. Our results support the notion of different cellular processing of αSyn and its contribution to the variability in seeding. This has implications for understanding disease progression, interpretation of seed amplification assays, and opens avenues for the development of cell type-specific antibodies against αSyn.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70024"},"PeriodicalIF":5.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309553","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}

引用次数: 0