Acta Neuropathologica最新文献

{"title":"Rapid brain lymphoma diagnostics through nanopore sequencing of cytology-negative cerebrospinal fluid","authors":"J. Hench, C. Hultschig, I. Bratic Hench, H. Sadasivan, Ö Yaldizli, G. Hutter, S. Dirnhofer, A. Tzankov, S. Frank","doi":"10.1007/s00401-024-02793-z","DOIUrl":"10.1007/s00401-024-02793-z","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioblastoma, IDH-wildtype with primarily leptomeningeal localization diagnosed by nanopore sequencing of cell-free DNA from cerebrospinal fluid","authors":"Nik Sol, Evert-Jan Kooi, Marc Pagès-Gallego, Dieta Brandsma, Marianna Bugiani, Jeroen de Ridder, Pieter Wesseling, Carlo Vermeulen","doi":"10.1007/s00401-024-02792-0","DOIUrl":"10.1007/s00401-024-02792-0","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum","authors":"Amanda E. Denning,&nbsp;Ranjit Ittyerah,&nbsp;Lisa M. Levorse,&nbsp;Niyousha Sadeghpour,&nbsp;Chinmayee Athalye,&nbsp;Eunice Chung,&nbsp;Sadhana Ravikumar,&nbsp;Mengjin Dong,&nbsp;Michael Tran Duong,&nbsp;Yue Li,&nbsp;Ademola Ilesanmi,&nbsp;Lasya P. Sreepada,&nbsp;Philip Sabatini,&nbsp;MaKayla Lowe,&nbsp;Alejandra Bahena,&nbsp;Jamila Zablah,&nbsp;Barbara E. Spencer,&nbsp;Ryohei Watanabe,&nbsp;Boram Kim,&nbsp;Maja Højvang Sørensen,&nbsp;Pulkit Khandelwal,&nbsp;Christopher Brown,&nbsp;Stanislau Hrybouski,&nbsp;Sharon X. Xie,&nbsp;Robin de Flores,&nbsp;John L. Robinson,&nbsp;Theresa Schuck,&nbsp;Daniel T. Ohm,&nbsp;Sanaz Arezoumandan,&nbsp;Sílvia Porta,&nbsp;John A. Detre,&nbsp;Ricardo Insausti,&nbsp;Laura E. M. Wisse,&nbsp;Sandhitsu R. Das,&nbsp;David J. Irwin,&nbsp;Edward B. Lee,&nbsp;David A. Wolk,&nbsp;Paul A. Yushkevich","doi":"10.1007/s00401-024-02789-9","DOIUrl":"10.1007/s00401-024-02789-9","url":null,"abstract":"<div><p>The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer’s disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. Our findings demonstrate the advantages of using quantitative neuropathology to understand the relationship of pathology to structure, particularly for p-tau, and motivate the use of quantitative pathology measurements in future studies.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic correlates of opioid-associated injury in CHANTER syndrome: first report of a post-mortem examination","authors":"Katherine E. Schwetye,&nbsp;Lakshmi Ramachandran Nair,&nbsp;Joseph Boyle,&nbsp;Jed A. Barash","doi":"10.1007/s00401-024-02797-9","DOIUrl":"10.1007/s00401-024-02797-9","url":null,"abstract":"<div><p>Opioid-associated brain injury may involve selective regions, including the hippocampi alone, globi pallidi, and cerebellar hemispheres. Opioid-associated amnestic syndrome, for example, is one clinical correlate of hippocampal injury as manifest by MRI abnormality. When all three regions are involved in what may be a more fulminant injury, the syndrome is termed “cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER)”, initially described in 2019. Until now, to our knowledge, there have been no histopathologic correlates to the imaging findings specifically in CHANTER syndrome. Here, for the first time, we present histopathologic findings of the post-mortem brain from a patient who died from complications of CHANTER syndrome following fentanyl intoxication. These observations included microhemorrhage, reactive and necrotic vasculature, eosinophilic neuronal necrosis, axonal swelling and spheroids, and frank infarction. The findings support previous experimental models implicating both hypoxic–ischemic and cytotoxic mechanisms in the tissue damage associated with CHANTER syndrome, though further work is needed to better characterize the exact cellular pathways involved to develop targeted treatments.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02797-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disability independent of cerebral white matter demyelination in progressive multiple sclerosis","authors":"Vikas Singh,&nbsp;Yufan Zheng,&nbsp;Daniel Ontaneda,&nbsp;Kedar R Mahajan,&nbsp;Jameson Holloman,&nbsp;Robert J Fox,&nbsp;Kunio Nakamura,&nbsp;Bruce D Trapp","doi":"10.1007/s00401-024-02796-w","DOIUrl":"10.1007/s00401-024-02796-w","url":null,"abstract":"<div><p>The pathogenic mechanisms contributing to neurological disability in progressive multiple sclerosis (PMS) are poorly understood. Cortical neuronal loss independent of cerebral white matter (WM) demyelination in myelocortical MS (MCMS) and identification of MS patients with widespread cortical atrophy and disability progression independent of relapse activity (PIRA) support pathogenic mechanisms other than cerebral WM demyelination. The three-dimensional distribution and underlying pathology of myelinated T2 lesions were investigated in postmortem MCMS brains. Postmortem brain slices from previously characterized MCMS (10 cases) and typical MS (TMS) cases (12 cases) were co-registered with <i>in situ</i> postmortem T2 hyperintensities and T1 hypointensities. T1 intensity thresholds were used to establish a classifier that differentiates MCMS from TMS. The classifier was validated in 36 uncharacterized postmortem brains and applied to baseline MRIs from 255 living PMS participants enrolled in SPRINT-MS. Myelinated T2 hyperintensities in postmortem MCMS brains have a contiguous periventricular distribution that expands at the occipital poles of the lateral ventricles where a surface-in gradient of myelinated axonal degeneration was observed. The MRI classifier distinguished pathologically confirmed postmortem MCMS and TMS cases with an accuracy of 94%. For SPRINT-MS patients, the MRI classifier identified 78% as TMS, 10% as MCMS, and 12% with a paucity of cerebral T1 and T2 intensities. In SPRINT-MS, expanded disability status scale and brain atrophy measures were similar in MCMS and TMS cohorts. A paucity of cerebral WM demyelination in 22% of living PMS patients raises questions regarding a primary role for cerebral WM demyelination in disability progression in all MS patients and has implications for clinical management of MS patients and clinical trial outcomes in PMS. Periventricular myelinated fiber degeneration provides additional support for surface-in gradients of neurodegeneration in MS.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02796-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRDM16-DT is a novel lncRNA that regulates astrocyte function in Alzheimer’s disease","authors":"Sophie Schröder,&nbsp;Ulrike Fuchs,&nbsp;Verena Gisa,&nbsp;Tonatiuh Pena,&nbsp;Dennis M. Krüger,&nbsp;Nina Hempel,&nbsp;Susanne Burkhardt,&nbsp;Gabriela Salinas,&nbsp;Anna-Lena Schütz,&nbsp;Ivana Delalle,&nbsp;Farahnaz Sananbenesi,&nbsp;Andre Fischer","doi":"10.1007/s00401-024-02787-x","DOIUrl":"10.1007/s00401-024-02787-x","url":null,"abstract":"<div><p>Astrocytes provide crucial support for neurons, contributing to synaptogenesis, synaptic maintenance, and neurotransmitter recycling. Under pathological conditions, deregulation of astrocytes contributes to neurodegenerative diseases such as Alzheimer’s disease (AD). While most research in this field has focused on protein-coding genes, non-coding RNAs, particularly long non-coding RNAs (lncRNAs), have emerged as significant regulatory molecules. In this study, we identified the lncRNA <i>PRDM16-DT</i> as highly enriched in the human brain, where it is almost exclusively expressed in astrocytes. <i>PRDM16-DT</i> and its murine homolog, <i>Prdm16os</i>, are downregulated in the brains of AD patients and in AD models. In line with this, knockdown of <i>PRDM16-DT</i> and <i>Prdm16os</i> revealed its critical role in maintaining astrocyte homeostasis and supporting neuronal function by regulating genes essential for glutamate uptake, lactate release, and neuronal spine density through interactions with the RE1-Silencing Transcription factor (Rest) and Polycomb Repressive Complex 2 (PRC2). Notably, CRISPR-mediated overexpression of <i>Prdm16os</i> mitigated functional deficits in astrocytes induced by stimuli linked to AD pathogenesis. These findings underscore the importance of <i>PRDM16-DT</i> in astrocyte function and its potential as a novel therapeutic target for neurodegenerative disorders characterized by astrocyte dysfunction.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02787-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory aspects of Alzheimer’s disease","authors":"Pablo Botella Lucena,&nbsp;Michael T. Heneka","doi":"10.1007/s00401-024-02790-2","DOIUrl":"10.1007/s00401-024-02790-2","url":null,"abstract":"<div><p>Alzheimer´s disease (AD) stands out as the most common chronic neurodegenerative disorder. AD is characterized by progressive cognitive decline and memory loss, with neurodegeneration as its primary pathological feature. The role of neuroinflammation in the disease course has become a focus of intense research. While microglia, the brain’s resident macrophages, have been pivotal to study central immune inflammation, recent evidence underscores the contributions of other cellular entities to the neuroinflammatory process. In this article, we review the inflammatory role of microglia and astrocytes, focusing on their interactions with AD’s core pathologies, amyloid beta deposition, and tau tangle formation. Additionally, we also discuss how different modes of regulated cell death in AD may impact the chronic neuroinflammatory environment. This review aims to highlight the evolving landscape of neuroinflammatory research in AD and underscores the importance of considering multiple cellular contributors when developing new therapeutic strategies.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between natural history and multi-omics profiling of meningiomas in NF2-related schwannomatosis suggests role of methylation group and immune microenvironment in tumor growth rate","authors":"Yu Teranishi,&nbsp;Andrey Yurchenko,&nbsp;Suzanne Tran,&nbsp;Philipp Sievers,&nbsp;Fatemeh Rajabi,&nbsp;Singhabahu Ruchith,&nbsp;Samiya Abi-Jaoude,&nbsp;Antoine Blouin,&nbsp;Franck Bielle,&nbsp;Dominique Cazals-Hatem,&nbsp;Felix Sahm,&nbsp;Sergey Nikolaev,&nbsp;Michel Kalamarides,&nbsp;Matthieu Peyre","doi":"10.1007/s00401-024-02791-1","DOIUrl":"10.1007/s00401-024-02791-1","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02791-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation profiling of plasma cell-free DNA in pediatric brain tumor patients","authors":"Shejuan An,&nbsp;Kathleen McCortney,&nbsp;Jordain Walshon,&nbsp;Kaethe Leonard,&nbsp;Brian Wray,&nbsp;Matthew McCord,&nbsp;Michael DeCuypere,&nbsp;Craig Horbinski","doi":"10.1007/s00401-024-02795-x","DOIUrl":"10.1007/s00401-024-02795-x","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02795-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-binding protein IGF2BP1 regulates stability of mRNA transcribed from FOXM1 target genes in hypermitotic meningiomas","authors":"Nathan K. Leclair,&nbsp;Calixto-Hope G. Lucas,&nbsp;Kanish Mirchia,&nbsp;Kathleen McCortney,&nbsp;Craig M. Horbinski,&nbsp;David R. Raleigh,&nbsp;Olga Anczukow","doi":"10.1007/s00401-024-02788-w","DOIUrl":"10.1007/s00401-024-02788-w","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02788-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}