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
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.
{"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":"<p>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. <i>KIAA1549-BRAF</i> tumors appeared more immunogenic, secreting higher levels of immune cell activators and chemokines, compared to <i>BRAF V600E</i> 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.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70023","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
<p>A 4-year-old female presented to the emergency department with persistent headaches, vomiting, and balance difficulties for 1 month. Neurological examination revealed significant ataxia and anisocoria. A posterior fossa heterogeneous mass with calcifications centered in the fourth ventricle was found, measuring approximately 5.0 × 4.7 × 4.2 cm (Figure 1). It was associated with severe supratentorial hydrocephalus. There was no evidence of spinal dissemination. She underwent placement of a right frontal external ventricular drain followed by suboccipital craniotomy and resection of the mass, with subsequent chemoradiation.</p><p>Histologic sections revealed a high-grade neoplasm with complex morphology. Some areas showed definite embryonal morphology with densely packed small cells with high nuclear/cytoplasmic ratio and brisk mitotic activity (Box 1, Figure 2A). The majority of the remaining tumor showed a mixture of haphazardly arranged spindled cell bundles with abundant eosinophilic cytoplasm and striations, typical of skeletal muscle differentiation (Figure 2B), and relatively mature neurons within a neuropil matrix, indicative of advanced neuronal differentiation (Figure 2C).</p><p>By immunohistochemistry (IHC), synaptophysin was positive in the embryonal component and areas with neuronal differentiation. Positive YAP1 stain was present and limited to the tumor cells with feature of skeletal muscle (Figure 2D). GAB1 stain was negative (Figure 2E), and beta-catenin expression was cytoplasmic (Figure 2F). Desmin, myogenin, and MyoD1 showed positivity in regions of skeletal muscle differentiation (Figure 2G,H). GFAP staining was largely confined to reactive astrocytes, while OLIG2 was negative. INI1 and BRG1 expressions were retained in the tumor cells. The IHC profile confirmed the morphological impression of medullomyoblastoma [<span>1</span>].</p><p>Chromosomal microarray and a Neuro-Oncology targeted next generation sequencing (NGS) panel were performed. The tumor showed partial gain of 1q and gain of chromosome 8, and harbored <i>KBTBD4</i> (p.R313_W315delinsGSATMR) and <i>SMARCA4</i> (p.R1189Q) pathogenic mutations. Two variants of uncertain significance (VUS) on <i>PDGFRA</i> (p.R293H) and <i>NTRK1</i> (p.V321M) were also present. These findings were most consistent with a non-WNT/non-SHH group 3/ group 4 medulloblastoma, favoring subgroup 2 [<span>2</span>].</p><p>Whole-genome methylation analysis performed at the Pathology Laboratory, National Cancer Institute using the Bethesda version 2 classifier yielded a “no match” result but suggested that the tumor belonged to the medulloblastoma family (Confidence Score [CS] = 0.909). Dimensionality reduction using UMAP (uniform manifold approximation and projection) positioned the tumor within a region enriched with medulloblastomas group 3/group 4, subgroup 2 (Figure 2I). Using the St. Jude methylation classifier, the tumor matched to group 3/group 4 medulloblastoma, subgroup 2, with high
{"title":"A posterior fossa mass in a 4-year-old female","authors":"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","doi":"10.1111/bpa.70028","DOIUrl":"10.1111/bpa.70028","url":null,"abstract":"<p>A 4-year-old female presented to the emergency department with persistent headaches, vomiting, and balance difficulties for 1 month. Neurological examination revealed significant ataxia and anisocoria. A posterior fossa heterogeneous mass with calcifications centered in the fourth ventricle was found, measuring approximately 5.0 × 4.7 × 4.2 cm (Figure 1). It was associated with severe supratentorial hydrocephalus. There was no evidence of spinal dissemination. She underwent placement of a right frontal external ventricular drain followed by suboccipital craniotomy and resection of the mass, with subsequent chemoradiation.</p><p>Histologic sections revealed a high-grade neoplasm with complex morphology. Some areas showed definite embryonal morphology with densely packed small cells with high nuclear/cytoplasmic ratio and brisk mitotic activity (Box 1, Figure 2A). The majority of the remaining tumor showed a mixture of haphazardly arranged spindled cell bundles with abundant eosinophilic cytoplasm and striations, typical of skeletal muscle differentiation (Figure 2B), and relatively mature neurons within a neuropil matrix, indicative of advanced neuronal differentiation (Figure 2C).</p><p>By immunohistochemistry (IHC), synaptophysin was positive in the embryonal component and areas with neuronal differentiation. Positive YAP1 stain was present and limited to the tumor cells with feature of skeletal muscle (Figure 2D). GAB1 stain was negative (Figure 2E), and beta-catenin expression was cytoplasmic (Figure 2F). Desmin, myogenin, and MyoD1 showed positivity in regions of skeletal muscle differentiation (Figure 2G,H). GFAP staining was largely confined to reactive astrocytes, while OLIG2 was negative. INI1 and BRG1 expressions were retained in the tumor cells. The IHC profile confirmed the morphological impression of medullomyoblastoma [<span>1</span>].</p><p>Chromosomal microarray and a Neuro-Oncology targeted next generation sequencing (NGS) panel were performed. The tumor showed partial gain of 1q and gain of chromosome 8, and harbored <i>KBTBD4</i> (p.R313_W315delinsGSATMR) and <i>SMARCA4</i> (p.R1189Q) pathogenic mutations. Two variants of uncertain significance (VUS) on <i>PDGFRA</i> (p.R293H) and <i>NTRK1</i> (p.V321M) were also present. These findings were most consistent with a non-WNT/non-SHH group 3/ group 4 medulloblastoma, favoring subgroup 2 [<span>2</span>].</p><p>Whole-genome methylation analysis performed at the Pathology Laboratory, National Cancer Institute using the Bethesda version 2 classifier yielded a “no match” result but suggested that the tumor belonged to the medulloblastoma family (Confidence Score [CS] = 0.909). Dimensionality reduction using UMAP (uniform manifold approximation and projection) positioned the tumor within a region enriched with medulloblastomas group 3/group 4, subgroup 2 (Figure 2I). Using the St. Jude methylation classifier, the tumor matched to group 3/group 4 medulloblastoma, subgroup 2, with high ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>A 19-year-old man presented with right eye ptosis, horizontal binocular diplopia, and right facial paresthesia. Neurological examination was consistent with right third, fourth, fifth, and sixth cranial neuropathies. Head MR imaging revealed multifocal leptomeningeal enhancement along bilateral cranial nerves and an enhancing mass at the right-sided prepontine cistern (Figure 1A). Chest and abdominal CT scans showed no significant abnormalities.</p><p>Three months later, he developed progressive bilateral lower extremity weakness. Spine MR imaging revealed diffuse leptomeningeal enhancement of the spinal cord and cauda equina, and enhancing intramedullary lesions at dorsal T4 and right-sided T10 thoracic levels (Figure 1B). Follow-up head MR imaging showed progressive leptomeningeal enhancement and newly developed ependymal enhancement in the fourth ventricle, frontal horns of bilateral lateral ventricles, and septum pellucidum.</p><p>An initial biopsy from the prepontine mass showed lymphohistiocytic proliferation with atypical cells, which, alongside immunohistochemical (IHC) testing, favored a benign histiocytic lesion. A bone marrow biopsy was negative for malignancy. Some cerebrospinal fluid (CSF) analyses revealed atypical mononuclear cells. A subsequent biopsy via L2 lumbar laminectomy showed lymphohistiocytic proliferation, comprising atypical histiocytes (positive for CD163 and CD68/PG-M1; negative for S100, CD1a, and ALK/ALK1/D5F3), together with Ki-67-positive atypical cells, small CD3-positive T cells, and small CD20-positive B cells (Figure 2A). In-situ hybridization (ISH) for Epstein–Barr virus early RNA (EBER) was negative.</p><p>Given the relentless clinical and radiological progression, a tentative diagnosis of malignant histiocytosis was made. The patient had been treated with multiple courses of high-dose methotrexate-based chemotherapy but showed negligible neurological improvement. He subsequently developed the neurogenic bladder with recurrent urinary tract infections and later obstructive hydrocephalus. Eventually, he received comfort care and died 33 months after the initial presentation.</p><p>At autopsy, the central nervous system (CNS) showed an infiltrative neoplasm extensively involving the craniospinal leptomeninges and ventricular system and invading the cranial nerves, spinal nerve roots, cauda equina, subpial brain/spinal cord parenchyma, and subependymal brain parenchyma (Box 1, Figure 2B). The non-cohesive large neoplastic cells had pleomorphic vesicular/hyperchromatic nuclei, prominent nucleoli, and abundant pale-eosinophilic cytoplasm (Figure 2C). There was high mitotic activity, multinucleated cell formation, hemophagocytic activity, apoptosis, and focal necrosis.</p><p>On IHC testing, most of the neoplastic cells were positive for CD163 (Figure 2D) and CD68/PG-M1 (Figure 2E). The neoplastic cells were negative for lysozyme, myeloperoxidase, CD1a, CD3, CD4, CD20, CD21, CD30, CD45/LCA, CD123, ALK/ALK1/D5F3,
{"title":"A young man with multifocal brainstem leptomeningeal disease","authors":"Burana Khiankaew, Pornphan Sae-Sim, Pichet Termsarasab, Oranan Tritanon, Theeraphol Panyaping, Paisarn Boonsakan, Vichan Peonim, Virawudh Soontornniyomkij","doi":"10.1111/bpa.70026","DOIUrl":"10.1111/bpa.70026","url":null,"abstract":"<p>A 19-year-old man presented with right eye ptosis, horizontal binocular diplopia, and right facial paresthesia. Neurological examination was consistent with right third, fourth, fifth, and sixth cranial neuropathies. Head MR imaging revealed multifocal leptomeningeal enhancement along bilateral cranial nerves and an enhancing mass at the right-sided prepontine cistern (Figure 1A). Chest and abdominal CT scans showed no significant abnormalities.</p><p>Three months later, he developed progressive bilateral lower extremity weakness. Spine MR imaging revealed diffuse leptomeningeal enhancement of the spinal cord and cauda equina, and enhancing intramedullary lesions at dorsal T4 and right-sided T10 thoracic levels (Figure 1B). Follow-up head MR imaging showed progressive leptomeningeal enhancement and newly developed ependymal enhancement in the fourth ventricle, frontal horns of bilateral lateral ventricles, and septum pellucidum.</p><p>An initial biopsy from the prepontine mass showed lymphohistiocytic proliferation with atypical cells, which, alongside immunohistochemical (IHC) testing, favored a benign histiocytic lesion. A bone marrow biopsy was negative for malignancy. Some cerebrospinal fluid (CSF) analyses revealed atypical mononuclear cells. A subsequent biopsy via L2 lumbar laminectomy showed lymphohistiocytic proliferation, comprising atypical histiocytes (positive for CD163 and CD68/PG-M1; negative for S100, CD1a, and ALK/ALK1/D5F3), together with Ki-67-positive atypical cells, small CD3-positive T cells, and small CD20-positive B cells (Figure 2A). In-situ hybridization (ISH) for Epstein–Barr virus early RNA (EBER) was negative.</p><p>Given the relentless clinical and radiological progression, a tentative diagnosis of malignant histiocytosis was made. The patient had been treated with multiple courses of high-dose methotrexate-based chemotherapy but showed negligible neurological improvement. He subsequently developed the neurogenic bladder with recurrent urinary tract infections and later obstructive hydrocephalus. Eventually, he received comfort care and died 33 months after the initial presentation.</p><p>At autopsy, the central nervous system (CNS) showed an infiltrative neoplasm extensively involving the craniospinal leptomeninges and ventricular system and invading the cranial nerves, spinal nerve roots, cauda equina, subpial brain/spinal cord parenchyma, and subependymal brain parenchyma (Box 1, Figure 2B). The non-cohesive large neoplastic cells had pleomorphic vesicular/hyperchromatic nuclei, prominent nucleoli, and abundant pale-eosinophilic cytoplasm (Figure 2C). There was high mitotic activity, multinucleated cell formation, hemophagocytic activity, apoptosis, and focal necrosis.</p><p>On IHC testing, most of the neoplastic cells were positive for CD163 (Figure 2D) and CD68/PG-M1 (Figure 2E). The neoplastic cells were negative for lysozyme, myeloperoxidase, CD1a, CD3, CD4, CD20, CD21, CD30, CD45/LCA, CD123, ALK/ALK1/D5F3,","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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.
{"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":"<p>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.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70025","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constantin Möller, Melanie Schoof, Keith L. Ligon, Ulrich Schüller
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.
{"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":"10.1111/bpa.70027","url":null,"abstract":"<p>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 <i>MGMT</i> 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.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70027","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ain Kim, Ivan Martinez-Valbuena, Krisztina Danics, Shelley L. Forrest, Gabor G. Kovacs
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.
{"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":"10.1111/bpa.70024","url":null,"abstract":"<p>Synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of misfolded <i>α</i>-synuclein (<i>α</i>Syn), predominantly in oligodendrocytes in multiple system atrophy (MSA) and in neurons in Lewy body diseases (LBD). The contribution of <i>α</i>Syn cytopathologies to the pathogenesis of these diseases is underappreciated. Seed amplification assays of MSA and LBD brains have revealed striking differences in <i>α</i>Syn seeding between regions and cases. Therefore, our aim was to evaluate whether different brain regions containing distinct <i>α</i>Syn cytopathologies contribute to different seeding characteristics. We collected 2-mm micro-punches of regions in MSA (<i>n</i> = 10) and LBD (<i>n</i> = 15) cases from formalin-fixed paraffin-embedded tissues. We performed double immuno-labeling for disease-associated <i>α</i>Syn and cellular markers on tissue microarrays, evaluated co-deposition of other neurodegenerative disease-related proteins and, from the same micro-punched samples, we analyzed <i>α</i>Syn 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 <i>α</i>Syn cytopathologies influence <i>α</i>Syn seeding patterns. Our results support the notion of different cellular processing of <i>α</i>Syn 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 <i>α</i>Syn.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70024","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bridget A. Ashford, Julie E. Simpson, Charlotte Dawson, Delphine Boche, Johnathan Cooper-Knock, Paul R. Heath, Daniel Fillingham, Charlie Appleby-Mallinder, Wenbin Wei, Mark Dunning, J. Robin Highley
A key role for inflammation in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been identified. It is vital to assess which central nervous system structures are most affected and which inflammatory processes are responsible in humans. The inflammatory transcriptome was characterized in the cervical spinal cord and motor cortex in post-mortem frozen and formalin-fixed paraffin-embedded specimens from human sporadic ALS/MND and control cases using the nCounter® Neuroinflammation Panel. Archival data were reanalyzed and compared with the nCounter data. Immunohistochemistry was used to examine the inflammatory response in the spinal cord and motor cortex and validate changes found during transcriptomic analyses. In the spinal cord, marked inflammation was observed, while less inflammation was detected in the motor cortex. Examination of differentially expressed genes in the spinal cord highlighted TREM2, TYROBP, APOE, and CD163, as well as phagocytic pathways. In sporadic ALS/MND spinal cord, significant microglial reactivity and involvement of TREM2, ApoE (encoded by APOE), and TYROBP were confirmed, suggesting the involvement of the disease-associated microglial (DAM) phenotype. The corticospinal tracts showed greater inflammation than the ventral horns. The precentral gyrus of ALS/MND again showed less immune reactivity to disease when compared to controls. Finally, in the largest cohort assessed to date, we demonstrate an association between the APOE variant and ALS/MND risk, age of onset, and survival. We find confirmed associations between APOE ε3/ε3 and disease and between ε2/ε2 and absence of disease. Further, ε4/ε4 appears to be associated with earlier disease onset and a more aggressive course. We conclude that while there is widespread inflammation in the CNS in sporadic ALS/MND, this is more marked in the spinal cord, especially the corticospinal tract. The specific markers stress the DAM phenotype as having a key role together with a possible influx of somatic macrophages. In addition, APOE function and genotype may be relevant in ALS/MND.
{"title":"Human amyotrophic lateral sclerosis/motor neuron disease: The disease-associated microglial pathway is upregulated while APOE genotype governs risk and survival","authors":"Bridget A. Ashford, Julie E. Simpson, Charlotte Dawson, Delphine Boche, Johnathan Cooper-Knock, Paul R. Heath, Daniel Fillingham, Charlie Appleby-Mallinder, Wenbin Wei, Mark Dunning, J. Robin Highley","doi":"10.1111/bpa.70019","DOIUrl":"10.1111/bpa.70019","url":null,"abstract":"<p>A key role for inflammation in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been identified. It is vital to assess which central nervous system structures are most affected and which inflammatory processes are responsible in humans. The inflammatory transcriptome was characterized in the cervical spinal cord and motor cortex in post-mortem frozen and formalin-fixed paraffin-embedded specimens from human sporadic ALS/MND and control cases using the nCounter® Neuroinflammation Panel. Archival data were reanalyzed and compared with the nCounter data. Immunohistochemistry was used to examine the inflammatory response in the spinal cord and motor cortex and validate changes found during transcriptomic analyses. In the spinal cord, marked inflammation was observed, while less inflammation was detected in the motor cortex. Examination of differentially expressed genes in the spinal cord highlighted <i>TREM2</i>, <i>TYROBP</i>, <i>APOE</i>, and <i>CD163</i>, as well as phagocytic pathways. In sporadic ALS/MND spinal cord, significant microglial reactivity and involvement of TREM2, ApoE (encoded by <i>APOE</i>), and TYROBP were confirmed, suggesting the involvement of the disease-associated microglial (DAM) phenotype. The corticospinal tracts showed greater inflammation than the ventral horns. The precentral gyrus of ALS/MND again showed less immune reactivity to disease when compared to controls. Finally, in the largest cohort assessed to date, we demonstrate an association between the <i>APOE</i> variant and ALS/MND risk, age of onset, and survival. We find confirmed associations between <i>APOE</i> ε3/ε3 and disease and between ε2/ε2 and absence of disease. Further, ε4/ε4 appears to be associated with earlier disease onset and a more aggressive course. We conclude that while there is widespread inflammation in the CNS in sporadic ALS/MND, this is more marked in the spinal cord, especially the corticospinal tract. The specific markers stress the DAM phenotype as having a key role together with a possible influx of somatic macrophages. In addition, <i>APOE</i> function and genotype may be relevant in ALS/MND.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emerging studies underscore the pivotal role of glymphatic system (GS) dysfunction in the pathogenesis of cerebral edema following brain injury. The transient receptor potential vanilloid 4 (TRPV4) channels have been implicated in modulating the polarization of aquaporin-4 (AQP4), a key protein involved in GS function. This study investigates the potential of targeting TRPV4 to alleviate GS dysfunction and reduce cerebral edema following ischemic stroke. TRPV4 inhibitor HC067047 or a vehicle was administered via lateral ventricle cannulation in a mouse model of middle cerebral artery occlusion and reperfusion (MCAO/R). The function of the GS was assessed through tracer injection experiments, including in vivo transcranial imaging, ex vivo brain tissue and section analysis, and fluorescence retention in deep cervical lymph nodes (dCLNs). Cerebral edema was quantified using magnetic resonance imaging. AQP4 polarization and β-dystroglycan (β-DG) expression were evaluated by immunofluorescence. Western blotting was employed to measure protein levels of β-DG, matrix metalloproteinase-9 (MMP9), and Ras homolog family member A (RhoA). Long-term neurological outcomes were assessed via behavioral testing. MCAO/R mice exhibited significant GS dysfunction, cerebral edema, and disrupted AQP4 polarization. Additionally, β-DG expression was markedly reduced, while TRPV4 expression was elevated in the ischemic penumbra. Western blotting revealed increased expression of MMP9 and RhoA. The inhibition of TRPV4 by HC067047 significantly improved GS function, reduced cerebral edema, and enhanced neurological recovery. Mechanistically, HC067047 partially restored AQP4 polarization, upregulated β-DG expression, and suppressed the expression of MMP9 and RhoA. These findings highlight the therapeutic potential of TRPV4 inhibition in ischemic stroke by restoring GS function, mitigating cerebral edema, and promoting neurological recovery, thereby positioning TRPV4 as a promising target for future interventions.
{"title":"Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke","authors":"Yongchuan Li, Haiping Zhou, Jiaxin Xie, Mingjia Yu, Guanyu Ye, Yuzhen Zhang, Zhentong Li, Kunxue Zhang, Jingwen Wu, Sheng Xiao, Shuxin Zeng, Yuan Chang, Kaibin Huang, Suyue Pan","doi":"10.1111/bpa.70022","DOIUrl":"10.1111/bpa.70022","url":null,"abstract":"<p>Emerging studies underscore the pivotal role of glymphatic system (GS) dysfunction in the pathogenesis of cerebral edema following brain injury. The transient receptor potential vanilloid 4 (TRPV4) channels have been implicated in modulating the polarization of aquaporin-4 (AQP4), a key protein involved in GS function. This study investigates the potential of targeting TRPV4 to alleviate GS dysfunction and reduce cerebral edema following ischemic stroke. TRPV4 inhibitor HC067047 or a vehicle was administered via lateral ventricle cannulation in a mouse model of middle cerebral artery occlusion and reperfusion (MCAO/R). The function of the GS was assessed through tracer injection experiments, including in vivo transcranial imaging, ex vivo brain tissue and section analysis, and fluorescence retention in deep cervical lymph nodes (dCLNs). Cerebral edema was quantified using magnetic resonance imaging. AQP4 polarization and β-dystroglycan (β-DG) expression were evaluated by immunofluorescence. Western blotting was employed to measure protein levels of β-DG, matrix metalloproteinase-9 (MMP9), and Ras homolog family member A (RhoA). Long-term neurological outcomes were assessed via behavioral testing. MCAO/R mice exhibited significant GS dysfunction, cerebral edema, and disrupted AQP4 polarization. Additionally, β-DG expression was markedly reduced, while TRPV4 expression was elevated in the ischemic penumbra. Western blotting revealed increased expression of MMP9 and RhoA. The inhibition of TRPV4 by HC067047 significantly improved GS function, reduced cerebral edema, and enhanced neurological recovery. Mechanistically, HC067047 partially restored AQP4 polarization, upregulated β-DG expression, and suppressed the expression of MMP9 and RhoA. These findings highlight the therapeutic potential of TRPV4 inhibition in ischemic stroke by restoring GS function, mitigating cerebral edema, and promoting neurological recovery, thereby positioning TRPV4 as a promising target for future interventions.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastomas represent the most common and lethal primary brain tumors in the world. Despite therapeutic advances during the last two decades, patient prognosis remains very poor. The Hippo signaling pathway effectors YAP/TAZ-TEADs play a crucial role in tumor progression and represent promising therapeutic targets in gliomas. In this study, we identified and investigated the clinical and biological significance of TEAD transcription factors. Through comprehensive analyses of TCGA glioma data and patient samples, we identified TEAD3-4 transcription factors as robust prognostic markers of patient outcome. Using up to five different patient-derived glioblastoma stem cell cultures, we confirmed the preferential expression and activation of TEAD3-4 along with their transcriptional coactivators YAP/TAZ. Pharmacological inhibition of YAP/TAZ-TEAD interaction by Verteporfin significantly decreased tumor cell growth, whereas specific inhibition of TEAD3 did not impact cell proliferation but affected sterol/cholesterol biosynthetic and metabolic processes. This study contributes to a better understanding of the role of Hippo effectors in glioblastoma pathophysiology. These transcription factors, particularly TEAD3, could potentially serve as therapeutic targets, especially considering recent data on cholesterol homeostasis in glioblastomas.
{"title":"Hippo pathway effectors are associated with glioma patient survival, control cell proliferation and sterol metabolism through TEAD3","authors":"Konstantin Masliantsev, Amandine Desette, Anne-Alicia Gonzalez, Inès Garrouche, Anaïs Noblanc, Maleaume Soulard, Mathis Triquard, Serge Milin, Michel Wager, Lucie Karayan-Tapon, Pierre-Olivier Guichet","doi":"10.1111/bpa.70021","DOIUrl":"10.1111/bpa.70021","url":null,"abstract":"<p>Glioblastomas represent the most common and lethal primary brain tumors in the world. Despite therapeutic advances during the last two decades, patient prognosis remains very poor. The Hippo signaling pathway effectors YAP/TAZ-TEADs play a crucial role in tumor progression and represent promising therapeutic targets in gliomas. In this study, we identified and investigated the clinical and biological significance of TEAD transcription factors. Through comprehensive analyses of TCGA glioma data and patient samples, we identified TEAD3-4 transcription factors as robust prognostic markers of patient outcome. Using up to five different patient-derived glioblastoma stem cell cultures, we confirmed the preferential expression and activation of TEAD3-4 along with their transcriptional coactivators YAP/TAZ. Pharmacological inhibition of YAP/TAZ-TEAD interaction by Verteporfin significantly decreased tumor cell growth, whereas specific inhibition of TEAD3 did not impact cell proliferation but affected sterol/cholesterol biosynthetic and metabolic processes. This study contributes to a better understanding of the role of Hippo effectors in glioblastoma pathophysiology. These transcription factors, particularly TEAD3, could potentially serve as therapeutic targets, especially considering recent data on cholesterol homeostasis in glioblastomas.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><b>The ISN is looking for a group of young motivated neuropathologists</b> to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (<span>[email protected]</span>) or Monika Hofer (<span>[email protected]</span>).</p><p><b>The International Congress of Neuropathology (ICN)</b> will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).</p><p>“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.</p><p>Colin Smith</p><p>Congress President ISN 2027”</p><p>Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).</p><p>We are delighted to start the bidding process for holding the <b>2031 XXII International Congress of Neuropathology (ICN)</b>. As you know, the 2027 XXI ICN Congress will be in Edinburgh and we now need to think ahead to 2031 and find a new home for our much-loved congress.</p><p>The Invitation Letter calling for bids and outlining the process can be found on the ISN website (www.intsocneuropathol.com). Please note that the deadline is the <b>31st August 2025</b>.</p><p>The <b>7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies</b> will be held in conjunction with the 30th Annual Meeting & Education Day of the Society for Neuro-Oncology <b>November 19-23, 2025</b> in Honolulu, Hawaii.</p><p><b><i>Brain Pathology has joined Wiley's Open Access</i></b> portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.</p><p><b>Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich</b>. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested
{"title":"SOCIETY NEWS","authors":"Audrey Rousseau","doi":"10.1111/bpa.70020","DOIUrl":"10.1111/bpa.70020","url":null,"abstract":"<p><b>The ISN is looking for a group of young motivated neuropathologists</b> to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (<span>[email protected]</span>) or Monika Hofer (<span>[email protected]</span>).</p><p><b>The International Congress of Neuropathology (ICN)</b> will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).</p><p>“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.</p><p>Colin Smith</p><p>Congress President ISN 2027”</p><p>Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).</p><p>We are delighted to start the bidding process for holding the <b>2031 XXII International Congress of Neuropathology (ICN)</b>. As you know, the 2027 XXI ICN Congress will be in Edinburgh and we now need to think ahead to 2031 and find a new home for our much-loved congress.</p><p>The Invitation Letter calling for bids and outlining the process can be found on the ISN website (www.intsocneuropathol.com). Please note that the deadline is the <b>31st August 2025</b>.</p><p>The <b>7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies</b> will be held in conjunction with the 30th Annual Meeting & Education Day of the Society for Neuro-Oncology <b>November 19-23, 2025</b> in Honolulu, Hawaii.</p><p><b><i>Brain Pathology has joined Wiley's Open Access</i></b> portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.</p><p><b>Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich</b>. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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