Brain Pathology最新文献

{"title":"A pineal mass in a 39-year-old woman.","authors":"Charlotte Paoli, Thibault Fabas, Lydiane Mondot, Catherine Godfraind, Bérengère Dadone-Montaudié, Fanny Burel-Vandenbos","doi":"10.1111/bpa.70012","DOIUrl":"https://doi.org/10.1111/bpa.70012","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70012"},"PeriodicalIF":5.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961698","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":"Stereological analysis of cholinergic neurons within bilateral pedunculopontine nuclei in health and when affected by Parkinson's disease.","authors":"Puneet Kumar Sharma, Steve Gentleman, David Trevor Dexter, Ilse Sanet Pienaar","doi":"10.1111/bpa.70011","DOIUrl":"https://doi.org/10.1111/bpa.70011","url":null,"abstract":"<p><p>During Parkinson's disease (PD), loss of brainstem-based pedunculopontine nucleus' (PPN) cholinergic neurons induces progressive postural-gait disability (PGD). PPN-deep brain stimulation inconsistently alleviates PGD, due to stereotactic targeting inaccuracies resulting from insufficiently detailed human PPN anatomical descriptions. Relatedly, rodent studies show rostro-caudal clustering of PPN-cholinergic neurons, reflecting functional sub-territories. We applied unbiased cerebro-bilateral 3-dimensional (3-D) stereology to post-mortem PPNs from PD versus neurological-control cases, to estimate total numbers of cholinergic neurons and describe their rostro-caudal distribution. Given ambiguous descriptions of the PPN's confines, we utilized two complimentary definitions of the PPN's anatomical boundaries. The first was based on the structure's gross anatomy, by considering the nucleus as a recognizable \"channel\" enclosed by distinct white matter fiber tracts (WMFT) encompassing the medial lemniscus, central tegmental tract and decussation of the superior cerebellar peduncle. Second, the PPN was recognized by its histological architecture, as a dense collection of cholinergic neurons (the \"Ch5\" group) that were immunoreactive for choline acetyltransferase (ChAT), the enzyme responsible for biosynthesis of the neurotransmitter acetylcholine. Many such ChAT-immunoreactive neurons were dispersed within the traversing tracks and hence the PPN's Ch5-based outlining method permitted their stereological capture while also allowing distinction between the PPN's two subnuclei, namely the pars compacta (PPNc) and pars dissipata (PPNd), based on subnuclei-specific cholinergic cytoarchitectural organization. We further reconstructed template data as 3-D renders, revealing gross morphological differences between control and PD-affected PPNs. PD brains revealed significant PPN cholinergic neuronal loss, particularly affecting the PPNd. Control cases showed bimodal clustering of cholinergic neurons, prominently affecting left-sided PPNs. Most PD cases revealed more severe cholinergic neuronal loss in right-sided PPNs, potentially driving symptom lateralization. Our study provides a comprehensive cholinergic cytoarchitectural atlas of the human PPN in health versus during PD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70011"},"PeriodicalIF":5.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954782","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":"Quantitative T1 is sensitive to cortical remyelination in multiple sclerosis: A postmortem MRI study.","authors":"Riccardo Galbusera, Matthias Weigel, Erik Bahn, Sabine Schaedelin, Alessandro Cagol, Po-Jui Lu, Muhamed Barakovic, Lester Melie-Garcia, Jonas Franz, Peter Dechent, Govind Nair, Ludwig Kappos, Wolfgang Brück, Christine Stadelmann, Cristina Granziera","doi":"10.1111/bpa.70010","DOIUrl":"https://doi.org/10.1111/bpa.70010","url":null,"abstract":"<p><p>Remyelination of cortical lesions in people with multiple sclerosis (pwMS) has been shown to be extensive. In this work, we aimed to assess whether postmortem quantitative MRI (qMRI) can help detect those areas. We imaged six fixed whole brains of deceased pwMS by 3T-MRI using magnetization transfer ratio (MTR, 570 μm isotropic), myelin water fraction (MWF, 1000 μm isotropic), quantitative T1 (qT1, 670 μm isotropic), quantitative susceptibility mapping (QSM, 330 μm isotropic) and radial diffusivity (RD, 1300 or 1400 μm isotropic) maps. Immunohistochemistry for myelin proteins was performed in 129 tissue blocks including the cortex and enabled the detection of cortical demyelination (DM), cortical remyelination (RM), and normal-appearing cortex (NAC). We identified 25 DM, 25 RM, and for each of these areas, a corresponding NAC near the lesion. Wilcoxon paired tests showed that: (a) qT1 and RD were higher and QSM lower in DM versus NAC (all p < 0.001), whereas RD was higher and QSM lower in RM versus NAC (p = 0.048 and p < 0.01 respectively); (b) mean qT1 in RM did not differ from mean qT1 in NAC (p = 0.074); (c) MWF and MTR were not different between DM and RM. We compared the delta between DM versus NAC (∆DM) and the delta between RM versus NAC (∆RM) using a Mann-Whitney test, in which RM showed a partial recovery of qT1 only (∆qT1 DM > ∆qT1 RM, p = 0.045). Mixed-effect models confirmed the findings obtained using univariate analyses. qT1 and QSM, but not RD, correlated with MBP intensity (r = -0.28, p < 0.01 and r = 0.29, p < 0.01 respectively). A Bonferroni correction was performed for multiple testing. Our data show that qT1 is altered in demyelinated but not in remyelinated cortical areas, while QSM and RD are affected by any cortical abnormalities. Accordingly, qT1 might be considered a potential imaging biomarker of cortical RM.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70010"},"PeriodicalIF":5.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979056","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":"A 23-year-old woman with a headache and imbalance.","authors":"Lukas Marcelis, Andrew Folpe, Sounak Gupta, Cinthya J Zepeda Mendoza","doi":"10.1111/bpa.70008","DOIUrl":"https://doi.org/10.1111/bpa.70008","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70008"},"PeriodicalIF":5.8,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751206","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":"Herpes simplex virus-1 infection alters microtubule-associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease.","authors":"Emmanuel C Ijezie, Michael J Miller, Celine Hardy, Ava R Jarvis, Timothy F Czajka, Lianna D'Brant, Natasha Rugenstein, Adam Waickman, Eain Murphy, David C Butler","doi":"10.1111/bpa.70006","DOIUrl":"10.1111/bpa.70006","url":null,"abstract":"<p><p>Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker of AD is the hyperphosphorylation of Tau, accompanied by altered levels of Tau isoforms. However, an imbalance in these Tau splice variants, specifically resulting from altered 3R to 4R MAPT splicing of exon 10, has yet to be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models with HSV-1 and monitored MAPT splicing and Tau phosphorylation. Further, we transduced SH-SY5Y neurons with HSV-1 ICP27, which alters RNA splicing, to analyze if ICP27 alone is sufficient to induce altered MAPT exon 10 splicing. We show that HSV-1 infection induces altered splicing of MAPT exon 10, increasing 4R-Tau protein levels, Tau hyperphosphorylation, and Tau oligomerization. Our experiments reveal a novel link between HSV-1 infection and the development of cytopathic phenotypes linked with AD progression.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70006"},"PeriodicalIF":5.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718007","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":"Multiple intracranial hemorrhages in a postmenopausal female","authors":"Xinhua Lu,&nbsp;Xinya Xu,&nbsp;Xiaopeng Zhang","doi":"10.1111/bpa.70007","DOIUrl":"10.1111/bpa.70007","url":null,"abstract":"&lt;p&gt;A 53-year-old postmenopausal female presented to the neurology clinic with acute onset of right arm weakness for 1 week. Neurologic examination was notable for 4/5 strength in the right upper extremity. Computed tomography revealed multiple hematomas with mass effect in the left frontal lobe and basal ganglia (Figure 1A; Box 1). Magnetic resonance imaging with gadolinium showed multiple heterogeneously enhancing lesions associated with surrounding edema, mass effect, and midline shift (Figure 1B). Given the absence of an overt primary source for the hemorrhagic mass with elevated intracranial pressure and neurologic deficits, surgical excision of the left frontal lobe lesion was performed. Intraoperatively, the mass showed evidence of prior hemorrhage and was noted to encase a relatively large vessel. Postoperative CT imaging showed gross total resection of the frontal lesion and found a new lesion adjacent to the left lateral ventricle (Figure 1A inset). Of notice in the past medical history, the patient had undergone hysterectomy 3 years earlier. After a final diagnosis was reached, adjuvant treatment was performed with stereotactic radiosurgery (SRS) and chemotherapy. At 10 months of follow-up, the patient's symptoms have resolved.&lt;/p&gt;&lt;p&gt;Hematoxylin–eosin stain showed that several pieces of tissue mingled together with a lot of blood. There was no normal brain parenchyma found. Small clusters of atypical cells made up of uninucleate and multinucleated cells were embedded in the hemorrhagic material. These were big cells with clumped chromatin, noticeable nucleoli, uneven nuclear outlines and nuclear-cytoplasmic ratios, and a modest proportion of amphophilic cytoplasm. Eosinophilic hyaline globules were seen in a large number of the cells. Mitoses were present (Figure 2A,B). Moreover, we saw atypical cells infiltrating relatively large vessels (Figure 2A) and some small vessels. Looking carefully into the previous history of hysterectomy, we found the diagnosis of complete hydatidiform mole, which led us to consider the possibility of metastatic gestational trophoblastic neoplasia (GTN). The atypical cells were strongly and diffusely positive for CK7 (Figure 2C) and β-HCG (Figure 2D), slightly immunopositive for SALL-4 (Figure 2E) on immunohistochemical examination. Ki-67 displayed a high proliferative index (approximately 60%, Figure 2F).&lt;/p&gt;&lt;p&gt;Metastatic gestational choriocarcinoma following complete hydatidiform mole.&lt;/p&gt;&lt;p&gt;Multiple intracranial hemorrhages can be due to a variety of causes, including hypertension, cerebral amyloid angiopathy (CAA), primary or secondary CNS vasculitis, hematologic disorders, anticoagulant use, sinus thrombosis, and brain tumors, most frequently metastatic. In this patient, normotensive, young for CAA, and overall only apparently without a significant past medical history, multiple hemorrhagic lesions on MRI led to the suspicion of brain metastases. Once discovered, the previous diagnosis of complete hydat","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699670","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":"Audrey Rousseau","doi":"10.1111/bpa.70009","DOIUrl":"https://doi.org/10.1111/bpa.70009","url":null,"abstract":"&lt;p&gt;&lt;b&gt;The ISN is looking for a group of young motivated neuropathologists&lt;/b&gt; to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (&lt;span&gt;[email protected]&lt;/span&gt;) or Monika Hofer (&lt;span&gt;[email protected]&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;The International Congress of Neuropathology (ICN)&lt;/b&gt; 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).&lt;/p&gt;&lt;p&gt;“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.&lt;/p&gt;&lt;p&gt;Colin Smith&lt;/p&gt;&lt;p&gt;Congress President ISN 2027”&lt;/p&gt;&lt;p&gt;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).&lt;/p&gt;&lt;p&gt;We are delighted to start the bidding process for holding the &lt;b&gt;2031 XXII International Congress of Neuropathology (ICN)&lt;/b&gt;. 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.&lt;/p&gt;&lt;p&gt;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 &lt;b&gt;31st August 2025&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;The &lt;b&gt;7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies&lt;/b&gt; will be held in conjunction with the 30th Annual Meeting &amp; Education Day of the Society for Neuro-Oncology &lt;b&gt;November 19-23, 2025&lt;/b&gt; in Honolulu, Hawaii.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Brain Pathology has joined Wiley's Open Access&lt;/i&gt;&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich&lt;/b&gt;. 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 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750004","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":"Spliceosome protein alterations differentiate hubs of the default mode connectome during the progression of Alzheimer's disease.","authors":"Sylvia E Perez, Muhammad Nadeem, Bin He, Jennifer C Miguel, David G Moreno, Marta Moreno-Rodriguez, Michael Malek-Ahmadi, Chadwick M Hales, Elliott J Mufson","doi":"10.1111/bpa.70004","DOIUrl":"10.1111/bpa.70004","url":null,"abstract":"<p><p>Default mode network (DMN) is comprised in part of the frontal (FC), precuneus (PreC), and posterior cingulate (PCC) cortex and displays amyloid and tau pathology in Alzheimer's disease (AD). The PreC hub appears the most resilient to AD pathology, suggesting differential vulnerability within the DMN. However, the mechanisms that underlie this differential pathobiology remain obscure. Here, we investigated changes in RNA polymerase II (RNA pol II) and splicing proteins U1-70K, U1A, SRSF2, and hnRNPA2B1, phosphorylated AT8 tau, 3R and 4Rtau isoforms containing neurons and amyloid plaques in layers III and V-VI in FC, PreC, and PCC obtained from individuals with a preclinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild/moderate mAD. We found a significant increase in pS5-RNA pol II levels in FC NCI, U1-70K in PreC MCI and mAD, and hnRNPA2B1 and SRSF2 levels in PCC mAD. 1N3Rtau levels were significantly increased in FC, decreased in PreC in mAD, and unchanged in PCC, whereas 1N4Rtau increased in mAD across the hubs. SRSF2, U1-70K, U1A, and hnRNPA2B1 nuclear optical density (OD), size, and number were unchanged across groups in FC and PCC, while PreC OD hnRNPA2B1 was significantly greater in mAD. Mislocalized U1A and U1-70K tangle-like structures were found in a few PCC cases and colocalized with AT8-bearing neurofibrillary tangles (NFTs). FC pS5-RNA pol II, PreC U1-70K, Pre pS5,2-RNA pol II, and PCC hnRNPA2B1 and SRSF2 protein levels were associated with cognitive decline but not neuropathology across clinical groups. By contrast, splicing protein nuclear OD measures, size, counts, and mislocalized U1-70K and U1A NFT-like structures were not correlated with NFT or plaque density, cognitive domains, and neuropathological criteria in DMN hubs. Findings suggest that RNA splicing protein alterations and U1 mislocalization contribute differentially to DMN pathogenesis and cognitive deterioration in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70004"},"PeriodicalIF":5.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691297","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":"Intraventricular mass in a 52-year-old woman","authors":"Felix Mircea Brehar,&nbsp;Alexandra Mihaela Pătrășcan,&nbsp;Mihaela Andreescu,&nbsp;Laura-Gabriela Țîrlea,&nbsp;Sabina-Loredana-Georgiana Olteanu,&nbsp;Simon Schallenberg,&nbsp;Mihnea P. Dragomir,&nbsp;George E. D. Petrescu","doi":"10.1111/bpa.70003","DOIUrl":"10.1111/bpa.70003","url":null,"abstract":"&lt;p&gt;A 52-year-old woman, without previous medical history, presented to our hospital with acute onset of headache, dizziness, and fatigability. Brain magnetic resonance imaging (MRI) revealed a 17.4 mm × 15.4 mm × 23.5 mm solitary, circumscribed, well-defined enhancing mass, centered on the trigone of the left lateral ventricle. Radiological findings were suggestive of intraventricular meningioma (Figure 1). The patient underwent surgery, and a gross total resection was performed. The intraoperative macroscopic findings were typical for a meningioma—the tumor was overly fibrous, well-defined, firm, encapsulated, and attached to the ventricular walls and choroid plexus.&lt;/p&gt;&lt;p&gt;Histological examination revealed a tumor composed of a mixture of diffuse infiltrates of medium-sized lymphocytes with rounded and angled nuclei and relatively abundant pale cytoplasm, and plasmacytoid cells with paracentric nuclei, wheel-like chromatin, and eosinophilic cytoplasm (Figure 2A, Box 1). A lymphoplasmacytic meningioma was suspected, and immunohistochemistry (IHC) was performed to confirm the diagnosis. The medium-sized lymphocytes mainly expressed CD20 (Figure 2B) and CD79a and were negative for CD5 (Figure 2C) and CD3; therefore, they could be assigned to the B-cell lineage, suggesting B-cell non-Hodgkin-lymphoma (B-NHL) accompanied by a physiological CD3, CD5 T-cell infiltrate. The B-lymphocytes and plasma cells also showed a monotypic expression of the immunoglobulin light chain kappa (kappa/lambda ratio: &gt;10/1, Figure 2D,E). Immunohistochemically, there was no evidence of aberrant expression of CD10, BCL6, CD23, CyclinD1, MUM1, EMA, or progesterone receptor and therefore, there was no evidence of B-CLL, mantle cell lymphoma, follicular lymphoma, or meningioma. The proliferation index (Ki-67) was low (~15%, Figure 2F), consistent with the diagnosis of indolent B-NHL.&lt;/p&gt;&lt;p&gt;Serum protein electrophoresis and immunofixation showed no serum immunoglobulin abnormalities. A sternal bone marrow biopsy was performed, with normal findings.&lt;/p&gt;&lt;p&gt;Primary intraventricular marginal zone B-cell lymphoma was diagnosed.&lt;/p&gt;&lt;p&gt;Extranodal marginal zone lymphoma (EMZL) is an indolent, small B-cell neoplasm that can be found in any extranodal location, but most frequently in the gastrointestinal tract (MALT lymphoma). [&lt;span&gt;1&lt;/span&gt;] In rare cases, MALT lymphomas may develop in tissues without mucosa, including the central nervous system. Ventricular invasion of a parenchymal primary CNS lymphoma occurs in up to 10.6% of cases, but an exclusively intraventricular form is very rare. [&lt;span&gt;1-3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;MALT lymphomas have the ability to mimic meningiomas on imaging, dural-based masses being the most common appearance. [&lt;span&gt;2&lt;/span&gt;] Despite the lack of mucosa in the brain tissue, it is suggested that intraventricular MALT lymphomas may be mistaken for meningiomas because arachnoid cap cells (contained within the choroid plexus) serve as a surrogate for mucosal epithel","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596259","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":"Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis.","authors":"Lauren Griffiths, Kristen Hawkins, Eylan Yutuc, Roberto Angelini, Racheal Fosuah, Manuela Pacciarini, Alison Dickson, Neil Robertson, Laura Childs, Samantha Loveless, Emma Tallantyre, William J Griffiths, Yuqin Wang, Owain W Howell","doi":"10.1111/bpa.70001","DOIUrl":"https://doi.org/10.1111/bpa.70001","url":null,"abstract":"<p><p>Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis is essential for normal brain function. CYP46A1, crucial for brain cholesterol turnover and reduced in some neurodegenerative diseases, is a potential neuroprotective target. We hypothesized that CYP46A1 is downregulated in MS brains and linked to cholesterol dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma and cerebrospinal fluid (CSF) in an all-female MS cohort (n = 32, mean age = 33). Disability status was recorded at baseline and follow-up. MS brain tissue samples (n = 11; 7 females; ages 38-67; 10 Secondary Progressive MS, 1 Primary Progressive MS; Disease Duration: 13-49 years) and control samples (n = 8; 3 females; ages 41-68) analysed for pathological regions using mass spectrometry and RNA expression using in-situ hybridization. Significant dysregulation in 25-hydroxycholesterol, 27-hydroxycholesterol and 3β-hydroxycholestenoic acid in CSF correlated with disability at baseline and follow-up in the patient population. In brain tissue, reduced cholesterol, 24S-hydroxycholesterol and 24S,25-epoxycholesterol were observed in white matter lesions (p < 0.05), linked to CYP46A1 activity. CYP46A1 expression was enriched in neurons, with reductions in MS grey matter lesions and non-lesions compared to controls (p < 0.01). Cholesterol metabolism is dysregulated in MS and is associated with reduced neuron-specific CYP46A1 expression. Modulating CYP46A1, a druggable target, may benefit progressive MS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70001"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566189","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}