Neuropathology and Applied Neurobiology最新文献

{"title":"Establishment and characterisation of STAM4, a novel human adamantinomatous craniopharyngioma cell line, through human telomerase reverse transcriptase ectopic expression-mediated immortalisation","authors":"Chaohu Wang, Huarong Zhang, Rongrong Guo, Ya'nan Cao, Jun Pan, Haoying Yu, Xiaoyu Qiu, Jin Shi, Jun Fan, Songtao Qi, Yi Liu","doi":"10.1111/nan.12958","DOIUrl":"https://doi.org/10.1111/nan.12958","url":null,"abstract":"Adamantinomatous craniopharyngioma (ACP) is a rare benign intracranial tumour that occurs in the sellar region and likely originates from the embryonic craniopharyngeal epithelium (a remnant of the ectoderm, also known as Rathke's pouch). However, progress in ACP research has been slow due to the lack of ACP cell lines. Therefore, in this study, we established an immortalised ACP cell line.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"4 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139552130","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}

{"title":"Pathogenic DPAGT1 variants in limb-girdle congenital myasthenic syndrome (LG-CMS) associated with tubular aggregates and ORAI1 hypoglycosylation","authors":"Laura Vanden Brande, Stéphanie Bauché, Laura Pérez-Guàrdia, Damien Sternberg, Andreea M. Seferian, Edoardo Malfatti, Roberto Silva-Rojas, Clémence Labasse, Frédéric Chevessier, Pierre Carlier, Bruno Eymard, Norma B. Romero, Jocelyn Laporte, Laurent Servais, Teresa Gidaro, Johann Böhm","doi":"10.1111/nan.12952","DOIUrl":"https://doi.org/10.1111/nan.12952","url":null,"abstract":"Limb-girdle congenital myasthenic syndrome (LG-CMS) is a genetically heterogeneous disorder characterized by muscle weakness and fatigability. The LG-CMS gene <i>DPAGT1</i> codes for an essential enzyme of the glycosylation pathway, a posttranslational modification mechanism shaping the structure and function of proteins. In <i>DPAGT1</i>-related LG-CMS, reduced glycosylation of the acetylcholine receptor (AChR) reduces its localization at the neuromuscular junction (NMJ), and results in diminished neuromuscular transmission. LG-CMS patients also show tubular aggregates on muscle biopsy, but the origin and potential contribution of the aggregates to disease development are not understood. Here, we describe two LG-CMS patients with the aim of providing a molecular diagnosis and to shed light on the pathways implicated in tubular aggregate formation.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"58 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825407","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}

{"title":"Molecular refinement of pilocytic astrocytoma in adult patients.","authors":"Helena Bode, Catena Kresbach, Dörthe Holdhof, Mario M Dorostkar, Patrick N Harter, Jürgen Hench, Stephan Frank, Abigail K Suwala, Leonille Schweizer, Alicia Eckhardt, Sina Neyazi, Michael Bockmayr, Annika K Wefers, Ulrich Schüller","doi":"10.1111/nan.12949","DOIUrl":"https://doi.org/10.1111/nan.12949","url":null,"abstract":"<p><strong>Aim: </strong>Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).</p><p><strong>Methods: </strong>We performed global DNA methylation profiling and DNA and RNA panel sequencing, and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier.</p><p><strong>Results: </strong>The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t-SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling.</p><p><strong>Conclusions: </strong>A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p<0.01).</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12949"},"PeriodicalIF":5.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808426","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}

{"title":"Filipin complex-reactive brain lesions: a cautionary tale.","authors":"Adeline A Lau, Paul J Trim, Barbara M King, Sofia Hassiotis, Ya Hui Hung, Ashley I Bush, Marten F Snel, Kim M Hemsley","doi":"10.1111/nan.12950","DOIUrl":"https://doi.org/10.1111/nan.12950","url":null,"abstract":"<p><strong>Objective: </strong>Filipin complex is an autooxidation-prone fluorescent histochemical stain used in the diagnosis of Niemann-Pick Disease Type C (NP-C), a neurodegenerative lysosomal storage disorder. It is also widely used by researchers examining the distribution and accumulation of unesterified cholesterol in cell and animal models of neurodegenerative diseases including NP-C and Sanfilippo syndrome (mucopolysaccharidosis IIIA; MPS IIIA). Recently, it has been suggested to be useful in studying Alzheimer's and Huntington's disease. Given filipin's susceptibility to photobleaching, we sought to establish a quantitative biochemical method for free cholesterol measurement.</p><p><strong>Methods: </strong>Brain tissue from mice with MPS IIIA was stained with filipin. Total and free cholesterol in brain homogenates was measured using a commercially available kit and a quantitative LC-MS/MS assay was developed. Gangliosides GM1, GM2 and GM3 were also quantified using LC-MS/MS.</p><p><strong>Results: </strong>As anticipated, the MPS IIIA mouse brain displayed large numbers of filipin-positive intra-cytoplasmic inclusions, presumptively endo-lysosomes. Challenging the prevailing dogma, however, we found no difference in the amount of free cholesterol in MPS IIIA mouse brain homogenates cf. control tissue, using either the fluorometric kit or LC-MS/MS assay. Filipin has previously been reported to bind to GM1 ganglioside, however, this lipid does not accumulate in MPS IIIA cells/tissues. Using a fluorometric assay, we demonstrate for the first time that filipin cross-reacts with both GM2 and GM3 gangliosides, explaining the filipin-reactive inclusions observed in MPS IIIA brain cells.</p><p><strong>Conclusion: </strong>Filipin is not specific for free cholesterol, and positive staining in any setting should be interpreted with caution.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12950"},"PeriodicalIF":5.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808424","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}

{"title":"Analysis of a pituitary tumour with histological features of central neurocytoma points towards the emergence of a new entity recognizable by a specific epigenetic signature.","authors":"Catherine Godfraind, Marie Coutelier, Daniel Pissaloux, Fabien Forest, Fanny Vandenbos, Martin Hasselblatt, Jean Boutonnat, Aurélien Coste, Sylvie Lantuejoul, Anne Mc Leer","doi":"10.1111/nan.12948","DOIUrl":"https://doi.org/10.1111/nan.12948","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12948"},"PeriodicalIF":5.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808423","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}

{"title":"LMNB1-duplication mediated nuclear architecture alteration and demyelination of cerebral white matter in a patient with ADLD.","authors":"Vincent Roy, Isabella Bienjonetti, Alyssa Brodeur, Laurence Dion-Albert, Lydia Touzel-Deschênes, Peter V Gould, Stephan Saikali, Robert Jr Laforce, François Gros-Louis","doi":"10.1111/nan.12947","DOIUrl":"https://doi.org/10.1111/nan.12947","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12947"},"PeriodicalIF":5.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808425","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}

{"title":"Identifying diagnostic and prognostic factors in cerebral amyloid angiopathy-related inflammation: a systematic analysis of published and seven new cases","authors":"Levente Szalardy, Bernadett Fakan, Rita Maszlag-Torok, Emil Ferencz, Zita Reisz, Bence L. Radics, Sandor Csizmadia, Laszlo Szpisjak, Adam Annus, Denes Zadori, Gabor G. Kovacs, Peter Klivenyi","doi":"10.1111/nan.12946","DOIUrl":"https://doi.org/10.1111/nan.12946","url":null,"abstract":"Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a potentially reversible manifestation of CAA, histopathologically characterised by transmural and/or perivascular inflammatory infiltrates. We aimed to identify clinical, radiological, and laboratory variables capable of improving or supporting the diagnosis of or predicting/influencing the prognosis of CAA-RI and to retrospectively evaluate different therapeutic approaches.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"7 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683455","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}

{"title":"Pediatric Anesthesia in the Community.","authors":"Richard P Dutton, Robert B Bryskin, Marion 'Red' Starks, Aesha S Shukla, Olivia Lounsbury","doi":"10.1016/j.aan.2023.06.002","DOIUrl":"10.1016/j.aan.2023.06.002","url":null,"abstract":"<p><p>Pediatric anesthesia is a diverse subspecialty practiced at thousands of hospitals and ambulatory surgery centers across the country. Most unusual and high-risk cases are performed in dedicated children's hospitals. However, the majority of cases and practitioners are based in the community. We present a review of demographics in pediatric anesthesia in the United States across 7 years of data from US Anesthesia Partners, a national anesthesia practice, which covers the full range of hospitals and outpatient facilities.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"1 1","pages":"127-142"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84954810","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}

{"title":"RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: Considerations for biomarker discovery.","authors":"Natalie Grima, Sidong Liu, Dean Southwood, Lyndal Henden, Andrew Smith, Albert Lee, Dominic B Rowe, Susan D'Silva, Ian P Blair, Kelly L Williams","doi":"10.1111/nan.12943","DOIUrl":"10.1111/nan.12943","url":null,"abstract":"<p><strong>Aim: </strong>Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether biomarkers for diagnosis, prognosis or cohort stratification could be identified by RNA sequencing (RNA-seq) of ALS patient peripheral blood.</p><p><strong>Methods: </strong>Whole blood RNA-seq data were generated for 96 Australian sporadic ALS (sALS) cases and 48 healthy controls (NCBI GEO accession GSE234297). Differences in sALS-control gene expression, transcript usage and predicted leukocyte proportions were assessed, with pathway analysis used to predict the activity state of biological processes. Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms were applied to search for diagnostic and prognostic gene expression patterns. Unsupervised clustering analysis was employed to determine whether sALS patient subgroups could be detected.</p><p><strong>Results: </strong>Two hundred and forty-five differentially expressed genes were identified in sALS patients relative to controls, with enrichment of immune, metabolic and stress-related pathways. sALS patients also demonstrated switches in transcript usage across a small set of genes. We established a classification model that distinguished sALS patients from controls with an accuracy of 78% (sensitivity: 79%, specificity: 75%) using the expression of 20 genes. Clustering analysis identified four patient subgroups with gene expression signatures and immune cell proportions reflective of distinct peripheral effects.</p><p><strong>Conclusions: </strong>Our findings suggest that peripheral blood RNA-seq can identify diagnostic biomarkers and distinguish molecular subtypes of sALS patients however, its prognostic value requires further investigation.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12943"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41207131","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}

{"title":"Quantitative cellular changes in multiple system atrophy brains.","authors":"Alberte M Andersen, Sanne S Kaalund, Lisbeth Marner, Lisette Salvesen, Bente Pakkenberg, Mikkel V Olesen","doi":"10.1111/nan.12941","DOIUrl":"10.1111/nan.12941","url":null,"abstract":"<p><p>Multiple system atrophy (MSA) is a neurodegenerative disorder characterised by a combined symptomatology of parkinsonism, cerebellar ataxia, autonomic failure and corticospinal dysfunction. In brains of MSA patients, the hallmark lesion is the aggregation of misfolded alpha-synuclein in oligodendrocytes. Even though the underlying pathological mechanisms remain poorly understood, the evidence suggests that alpha-synuclein aggregation in oligodendrocytes may contribute to the neurodegeneration seen in MSA. The primary aim of this review is to summarise the published stereological data on the total number of neurons and glial cell subtypes (oligodendrocytes, astrocytes and microglia) and volumes in brains from MSA patients. Thus, we include in this review exclusively the reports of unbiased quantitative data from brain regions including the neocortex, nuclei of the cerebrum, the brainstem and the cerebellum. Furthermore, we compare and discuss the stereological results in the context of imaging findings and MSA symptomatology. In general, the stereological results agree with the common neuropathological findings of neurodegeneration and gliosis in brains from MSA patients and support a major loss of nigrostriatal neurons in MSA patients with predominant parkinsonism (MSA-P), as well as olivopontocerebellar atrophy in MSA patients with predominant cerebellar ataxia (MSA-C). Surprisingly, the reports indicate only a minor loss of oligodendrocytes in sub-cortical regions of the cerebrum (glial cells not studied in the cerebellum) and negligible changes in brain volumes. In the past decades, the use of stereological methods has provided a vast amount of accurate information on cell numbers and volumes in the brains of MSA patients. Combining different techniques such as stereology and diagnostic imaging (e.g. MRI, PET and SPECT) with clinical data allows for a more detailed interdisciplinary understanding of the disease and illuminates the relationship between neuropathological changes and MSA symptomatology.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":"e12941"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145752","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}