Brain Pathology最新文献

{"title":"Meeting report of the 20th International Congress of Neuropathology (ICN) 2023 in Berlin","authors":"Hans H. Goebel, Arend Koch, Helena Radbruch, Simone Schmid, Ekaterina Friebel, Werner Stenzel, Frank L. Heppner, David Capper","doi":"10.1111/bpa.13249","DOIUrl":"10.1111/bpa.13249","url":null,"abstract":"<p>Exactly 62 years to the month after the 4th International Congress of Neuropathology (ICN) took place from September 4th to 8th 1961 at the Ludwig Maximilian University of Munich, the global neuropathological community—or, more accurately, its neuropathological children and grandchildren—returned back to the 20th ICN, that is, ICN2023, in Berlin/Germany (12–16 September 2023).</p><p>The archives of the International Society of Neuropathology (ISN), gainfully groomed by Maria Thom at University College, London/UK, provided extensive information on the scope, frame, and content of the earlier Munich ICN, which enabled a quick and insightful glimpse into the evolution of ICN between these two events, then and now.</p><p>In 1961, the documents of the 4th ICN were primarily produced in German and only secondly in English. Abstracts could only be submitted for oral presentations, as posters had not been “invented” but the submission languages were quite diverse, with abstracts in English, German, French, Italian, and Spanish. However, whether the multilingual presentations were delivered in the language as their titles suggested, remains unknown. Around 230 presentations were listed in the program and were held in two parallel sessions covering main topics according to different methodological techniques: “Histochemistry,” “Electron microscopy” and “Tissue culture” as well as “Free Communication” the entire content of which was subsequently published as “Proceedings” by Thieme Publishing Company [<span>1</span>]. The President of the International Committee of Neuropathology, Webb Haymaker from the United States, delivered a lengthy and solemn welcome opening address, presenting “perspectives on Neuropathology.” Following this, the local organizer and host of ICN1961, Willibald Scholz from Munich/Germany, and Hans Jacob, the General Secretary of ICN1961 from Marburg/Germany, addressed the audience. Recognition and merit awards were then presented to Armano Ferraro from New York City and Ludo van Bogaert from Antwerp. The presumably quite elaborate opening ceremony of ICN1961 was commented with a handwritten “Amen” in the archival papers by an unidentified critical reader. Two exhibitions, one with neuropathological slides and photographs, one with historical aspects of German Neuropathology, completed the scientific part of ICN1961. Socially, the participants were feasted to receptions hosted by the Bavarian State Government, the Mayor of Munich, a special opera performance of “Cosi fan tutte” at the Cuvillies Theater, and a gala banquet at the luxury hotel “Bayerischer Hof,” for a $15/20 registration fee and $5 for the banquet. A separate “Ladies' Program” encompassed a city tour, a visit to an antique collection, and a day tour to the tourist attraction “Wies-Kirche.” Finally, a post congress trip via Venice to the International Congress of Neurology in Rome was offered.</p><p>In 2016, at the European Congress of Neuropathology in Bordeaux, France","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989346","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":"Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights","authors":"Sergio Pérez-Oliveira,&nbsp;Juan Castilla-Silgado,&nbsp;Cèlia Painous,&nbsp;Iban Aldecoa,&nbsp;Manuel Menéndez-González,&nbsp;Marta Blázquez-Estrada,&nbsp;Daniela Corte,&nbsp;Cristina Tomás-Zapico,&nbsp;Yaroslau Compta,&nbsp;Esteban Muñoz,&nbsp;Albert Lladó,&nbsp;Mircea Balasa,&nbsp;Gemma Aragonès,&nbsp;Pablo García-González,&nbsp;Maitée Rosende-Roca,&nbsp;Mercè Boada,&nbsp;Agustín Ruíz,&nbsp;Pau Pastor,&nbsp;Beatriz De la Casa-Fages,&nbsp;Alberto Rabano,&nbsp;Raquel Sánchez-Valle,&nbsp;Laura Molina-Porcel,&nbsp;Victoria Álvarez","doi":"10.1111/bpa.13250","DOIUrl":"10.1111/bpa.13250","url":null,"abstract":"<p>Previous studies have suggested a relationship between the number of CAG triplet repeats in the <i>HTT</i> gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of <i>HTT</i> is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the <i>HTT</i> gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (<i>n</i>=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological <i>HTT</i> expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the <i>HTT</i> CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between <i>HTT</i> CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for <i>HTT</i> repeat expansions should be considered in tauopathies.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989345","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":"Society News","authors":"","doi":"10.1111/bpa.13241","DOIUrl":"https://doi.org/10.1111/bpa.13241","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139993955","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":"Ranking and filtering of neuropathology features in the machine learning evaluation of dementia studies","authors":"Mohammed D. Rajab,&nbsp;Teruka Taketa,&nbsp;Stephen B. Wharton,&nbsp;Dennis Wang,&nbsp;Cognitive Function and Ageing Neuropathology Study, and for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1111/bpa.13247","DOIUrl":"10.1111/bpa.13247","url":null,"abstract":"<p>Early diagnosis of dementia diseases, such as Alzheimer's disease, is difficult because of the time and resources needed to perform neuropsychological and pathological assessments. Given the increasing use of machine learning methods to evaluate neuropathology features in the brains of dementia patients, it is important to investigate how the selection of features may be impacted and which features are most important for the classification of dementia. We objectively assessed neuropathology features using machine learning techniques for filtering features in two independent ageing cohorts, the Cognitive Function and Aging Studies (CFAS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). The reliefF and least loss methods were most consistent with their rankings between ADNI and CFAS; however, reliefF was most biassed by feature–feature correlations. Braak stage was consistently the highest ranked feature and its ranking was not correlated with other features, highlighting its unique importance. Using a smaller set of highly ranked features, rather than all features, can achieve a similar or better dementia classification performance in CFAS (60%–70% accuracy with Naïve Bayes). This study showed that specific neuropathology features can be prioritised by feature filtering methods, but they are impacted by feature–feature correlations and their results can vary between cohort studies. By understanding these biases, we can reduce discrepancies in feature ranking and identify a minimal set of features needed for accurate classification of dementia.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905138","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":"A 7-year-old boy presented with temporal lobe lesion","authors":"Manli Zhao,&nbsp;Tingting Huang,&nbsp;Xueping Xiang,&nbsp;Yang Liu,&nbsp;Weizhong Gu,&nbsp;Lei Liu,&nbsp;Hongfeng Tang,&nbsp;Jinghong Xu,&nbsp;Jianhua Mao","doi":"10.1111/bpa.13246","DOIUrl":"10.1111/bpa.13246","url":null,"abstract":"&lt;p&gt;A previously healthy 7-year-old boy presented with generalized tonic-clonic seizures for approximately 1 month. He was the first child of unrelated, healthy parents and had exhibited normal development. MR imaging demonstrated a large, right-sided temporal lobe mass-like lesion measuring 44 × 25 × 24 mm. The lesion exhibited hypointense on T1-weighted images and a distinct heterogenous high signal intensity on T2/FLAIR images with nodular contrast enhancement (Figure 1). He underwent surgical gross total resection of the tumor and postoperatively he was free of symptoms. Eight months post-surgery, neuroimaging gave no indication of tumor recurrence.&lt;/p&gt;&lt;p&gt;Histological examination (Box 1) unveiled a lesion with two distinct morphological components: a highly cellular area in the superficial cortex and an area characterized by sparse cells in the central region (Figure 2). The highly cellular area consisted of dense spindle-shaped tumor cells with round to oval or irregular nuclei and scant cytoplasm. These cells were set against an edematous, myxoid, or collagenous background, and were diffusely distributed throughout (Figure 2A). The hypocellular area housed scattered calcification foci and a fibrillary matrix with sparsely distributed, yet unremarkable, infiltrative tumor cells possessing oval nuclei (Figure 2B). Both components contained occasional interspersed degenerating neurons and large reactive astrocytes. No rhabdoid cells were present. Mitotic figures could be identified in some regions of high cellularity (up to 5 mitotic figures in 10 visual fields at magnification 400×), but not in the hypocellular areas. Necrosis was not found.&lt;/p&gt;&lt;p&gt;The tumor cells showed negative INI1 expression. Interestingly, the reactivity was preserved in the degenerating neurons and reactive astrocytes (Figure 2C, D). The tumor cells were diffusely positive for vimentin, partially positive for CD34, yet remained negative for GFAP, Olig2, EMA, AE1/AE3, αSMA, S-100 protein, and NeuN. The degenerating neurons showed positive NeuN expression, while the large reactive astrocytes demonstrated immunoreactivity against GFAP and vimentin. Ki-67 labeling indices were noted at around 15% and 0.5% in the hypercellular and hypocellular areas, respectively (Figure 2E, F).&lt;/p&gt;&lt;p&gt;Applying a DNA methylation-based classification, the tumor was classified as AT/RT-MYC (with calibrated scores of 0.96). A homozygous SMARCB1/INI1 deletion was indicated through copy number analysis using DNA methylation array data, and this was further validated by fluorescence in situ hybridization.&lt;/p&gt;&lt;p&gt;Low-grade diffusely infiltrative tumor (LGDIT), SMARCB1-deficient, with high-grade component.&lt;/p&gt;&lt;p&gt;Central nervous system LGDIT with SMARCB1/INI1-deficiency has been proposed as a new entity in recent literatures [&lt;span&gt;1, 2&lt;/span&gt;]. Intriguingly, despite the loss of INI1 expression, it demonstrates distinct clinical and histopathological features, distinguishing it from atypical teratoid/rha","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734510","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":"Astrocyte-derived Interleukin-31 causes poor prognosis in elderly patients with intracerebral hemorrhage","authors":"Rui Jiang,&nbsp;Zhichao Lu,&nbsp;Chenxing Wang,&nbsp;WenJun Tu,&nbsp;Qi Yao,&nbsp;Jiabing Shen,&nbsp;Xingjia Zhu,&nbsp;Ziheng Wang,&nbsp;Yixun Chen,&nbsp;Yang Yang,&nbsp;Kaijiang Kang,&nbsp;Peipei Gong","doi":"10.1111/bpa.13245","DOIUrl":"10.1111/bpa.13245","url":null,"abstract":"<p>The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734511","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":"A 24-year-old woman with a recurrent intracranial mass","authors":"Yan Peng,&nbsp;Wei Zhao,&nbsp;Dachuan Zhang,&nbsp;Xie Gao,&nbsp;Yongqiang Shi,&nbsp;Qing Li,&nbsp;Jian Wang","doi":"10.1111/bpa.13242","DOIUrl":"10.1111/bpa.13242","url":null,"abstract":"&lt;p&gt;A 24-year-old woman presented with headache, dizziness, and tinnitus that had lasted for 3 months. Pre-operative magnetic resonance imaging (MRI) demonstrated a 6 × 4.9 × 4.3 cm well-circumscribed mass located in the right frontal lobe adjacent to the cerebral falx. The mass showed heterogeneous signal intensity and both solid and cystic components with perilesional brain edema on T1-weighted (Figure 1A) and T2-weighted images. Microsurgical tumor resection was performed. During the operation, it was found that the tumor originated from the falx and had infiltrated the opposite side. Gross total resection of the tumor was achieved with the adherent falx. The patient received no adjuvant treatment after the operation and had local recurrence 26 months after surgery, marked by the presence of headache. MRI demonstrated a 4.5 × 3.0 × 2.9 cm cystic-solid mass at the local recurrence (Figure 1B). The patient underwent gross total resection again and had a disease-free survival time of 14 months.&lt;/p&gt;&lt;p&gt;Histopathological examination revealed similar morphological features in both primary and recurrent tumors (Box 1). A fibrous pseudocapsule was present at the periphery of both tumors, which showed solid tumor cell nodules. A dense lymphoplasmacytic infiltrate with lymphoid follicles was present along the pseudocapsule and the periphery of the nodules (Figure 2A), which led to our first consideration of angiomatoid fibrous histiocytoma (AFH). Blood-filled pseudoangiomatoid cystic spaces and intratumor hemorrhage with hemosiderin were identified. Tumor cell morphology mainly included epithelioid, rhabdoid (Figure 2B), oval, and spindle morphology. Epithelioid cells embedded in a dense sclerotic stroma were seen (Figure 2C). The tumor cells had indistinct cell borders and inconspicuous nucleoli. Mitotic activity was low. Immunohistochemistry, the tumor cells were diffusely positive for desmin (Figure 2D) and CD99, and some were positive for EMA (Figure 2E) and MUC4. Few cells presented weak expression of ALK. The tumor cells were negative for S100, CD34, CD31, STAT6, HMB45, CD21, CD68, Synaptophysin, Chromogranin, WT1. The Ki-67 index was 5%. Next-generation sequencing (NGS) revealed that the tumor harbored exon 7 of the FUS gene and exon 6 of the CREM gene fusion (Figure 2F).&lt;/p&gt;&lt;p&gt;Intracranial mesenchymal tumor, &lt;i&gt;FET::CREB&lt;/i&gt; fusion-positive.&lt;/p&gt;&lt;p&gt;FET family (EWSR1 and FUS) fusions with CREB family (CREB1, CREM, and ATF1) are found in a wide variety of tumor entities. Kao et al [&lt;span&gt;1&lt;/span&gt;] first reported the occurrence of a unique myxoid mesenchymal tumor with &lt;i&gt;EWSR1&lt;/i&gt; fusions with &lt;i&gt;CREB&lt;/i&gt; family members in young patients with intracranial predilection in 2017. Previous studies speculated that these tumors may represent a myxoid variant of AFH occurring intracranially or a novel intracranial myxoid mesenchymal tumor (IMMT). Sloan et al. [&lt;span&gt;2&lt;/span&gt;] studied the largest numbers of these tumors, reviewed previously reported cases, a","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691268","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":"Transient receptor potential vanilloid 1 inhibition reduces brain damage by suppressing neuronal apoptosis after intracerebral hemorrhage","authors":"Chien-Cheng Chen,&nbsp;Chia-Hua Ke,&nbsp;Chun-Hu Wu,&nbsp;Hung-Fu Lee,&nbsp;Yuan Chao,&nbsp;Min-Chien Tsai,&nbsp;Song-Kun Shyue,&nbsp;Szu-Fu Chen","doi":"10.1111/bpa.13244","DOIUrl":"10.1111/bpa.13244","url":null,"abstract":"<p>Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades and inflammatory responses, leading to neurological impairment. Transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel with high calcium permeability, has been implicated in neuronal apoptosis and inflammatory responses. This study used a mouse ICH model and neuronal cultures to examine whether TRPV1 activation exacerbates brain damage and neurological deficits by promoting neuronal apoptosis and neuroinflammation. ICH was induced by injecting collagenase in both wild-type (WT) C57BL/6 mice and TRPV1^−/− mice. Capsaicin (CAP; a TRPV1 agonist) or capsazepine (a TRPV1 antagonist) was administered by intracerebroventricular injection 30 min before ICH induction in WT mice. The effects of genetic deletion or pharmacological inhibition of TRPV1 using CAP or capsazepine on motor deficits, histological damage, apoptotic responses, blood–brain barrier (BBB) permeability, and neuroinflammatory reactions were explored. The antiapoptotic mechanisms and calcium influx induced by TRPV1 inactivation were investigated in cultured hemin-stimulated neurons. TRPV1 expression was upregulated in the hemorrhagic brain, and TRPV1 was expressed in neurons, microglia, and astrocytes after ICH. Genetic deletion of TRPV1 significantly attenuated motor deficits and brain atrophy for up to 28 days. Deletion of TRPV1 also reduced brain damage, neurodegeneration, microglial activation, cytokine expression, and cell apoptosis at 1 day post-ICH. Similarly, the administration of CAP ameliorated brain damage, neurodegeneration, brain edema, BBB permeability, and cytokine expression at 1 day post-ICH. In primary neuronal cultures, pharmacological inactivation of TRPV1 by CAP attenuated neuronal vulnerability to hemin-induced injury, suppressed apoptosis, and preserved mitochondrial integrity in vitro. Mechanistically, CAP reduced hemin-stimulated calcium influx and prevented the phosphorylation of CaMKII in cultured neurons, which was associated with reduced activation of P38 and c-Jun NH₂-terminal kinase mitogen-activated protein kinase signaling. Our results suggest that TRPV1 inhibition may be a potential therapy for ICH by suppressing mitochondria-related neuronal apoptosis.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671314","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":"Apolipoprotein-E genotyping in formalin-fixed and paraffin-embedded post-mortem brain tissue","authors":"James Minshull,&nbsp;Yvonne Davidson,&nbsp;Federico Roncaroli,&nbsp;Andrew C. Robinson","doi":"10.1111/bpa.13243","DOIUrl":"10.1111/bpa.13243","url":null,"abstract":"<p>Formalin-fixed paraffin-embedded (FFPE) brain tissue held in tissue banks constitutes a valuable research resource, especially when associated with clinical annotations and longitudinal psychometric testing. Apolipoprotein-E (APOE) genotyping is important to fully characterise this resource, however older FFPE tissue may not be suitable for genotyping. We performed polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays on DNA extracted from post-mortem FFPE brain tissue ranging from 2-19 years old. A maximum of three years in paraffin was determined for robust APOE genotyping of FFPE tissue using PCR-RFLP which may suggest prolonged storage of fixed tissue as FFPE blocks may have deleterious effects on DNA.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545727","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":"The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis","authors":"Anja Steinmaurer,&nbsp;Christian Riedl,&nbsp;Theresa König,&nbsp;Giulia Testa,&nbsp;Ulrike Köck,&nbsp;Jan Bauer,&nbsp;Hans Lassmann,&nbsp;Romana Höftberger,&nbsp;Thomas Berger,&nbsp;Isabella Wimmer,&nbsp;Simon Hametner","doi":"10.1111/bpa.13240","DOIUrl":"10.1111/bpa.13240","url":null,"abstract":"<p>Activation of Bruton's tyrosine kinase (BTK) has been shown to play a crucial role in the proinflammatory response of B cells and myeloid cells upon engagement with B cell, Fc, Toll-like receptor, and distinct chemokine receptors. Previous reports suggest BTK actively contributes to the pathogenesis of multiple sclerosis (MS). The BTK inhibitor Evobrutinib has been shown to reduce the numbers of gadolinium-enhancing lesions and relapses in relapsing–remitting MS patients. In vitro, BTK inhibition resulted in reduced phagocytic activity and modulated BTK-dependent inflammatory signaling of microglia and macrophages. Here, we investigated the protein expression of BTK and CD68 as well as iron accumulation in postmortem control (<i>n</i> = 10) and MS (<i>n</i> = 23) brain tissue, focusing on microglia and macrophages. MS cases encompassed active, chronic active, and inactive lesions. BTK⁺ and iron⁺ cells positively correlated across all regions of interests and, along with CD68, revealed highest numbers in the center of active and at the rim of chronic active lesions. We then studied the effect of BTK inhibition in the human immortalized microglia-like HMC3 cell line in vitro. In particular, we loaded HMC3 cells with iron-dextran and subsequently administered the BTK inhibitor Evobrutinib. Iron treatment alone induced a proinflammatory phenotype and increased the expression of iron importers as well as the intracellular iron storage protein ferritin light chain (FTL). BTK inhibition of iron-laden cells dampened the expression of microglia-related inflammatory genes as well as iron-importers, whereas the iron-exporter ferroportin was upregulated. Our data suggest that BTK inhibition not only dampens the proinflammatory response but also reduces iron import and storage in activated microglia and macrophages with possible implications on microglial iron accumulation in chronic active lesions in MS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520201","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}