Acta Neuropathologica最新文献

{"title":"Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies","authors":"Luna Slemann,&nbsp;Johannes Gnörich,&nbsp;Selina Hummel,&nbsp;Laura M. Bartos,&nbsp;Carolin Klaus,&nbsp;Agnes Kling,&nbsp;Julia Kusche-Palenga,&nbsp;Sebastian T. Kunte,&nbsp;Lea H. Kunze,&nbsp;Amelie L. Englert,&nbsp;Yunlei Li,&nbsp;Letizia Vogler,&nbsp;Sabrina Katzdobler,&nbsp;Carla Palleis,&nbsp;Alexander Bernhardt,&nbsp;Alexander Jäck,&nbsp;Andreas Zwergal,&nbsp;Franziska Hopfner,&nbsp;Sebastian N. Roemer-Cassiano,&nbsp;Gloria Biechele,&nbsp;Sophia Stöcklein,&nbsp;Gerard Bischof,&nbsp;Thilo van Eimeren,&nbsp;Alexander Drzezga,&nbsp;Osama Sabri,&nbsp;Henryk Barthel,&nbsp;Gesine Respondek,&nbsp;Timo Grimmer,&nbsp;Johannes Levin,&nbsp;Jochen Herms,&nbsp;Lars Paeger,&nbsp;Marie Willroider,&nbsp;Leonie Beyer,&nbsp;Günter U. Höglinger,&nbsp;Sigrun Roeber,&nbsp;Nicolai Franzmeier,&nbsp;Matthias Brendel","doi":"10.1007/s00401-024-02834-7","DOIUrl":"10.1007/s00401-024-02834-7","url":null,"abstract":"<div><p>Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [¹⁸F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients. First, we conducted a longitudinal [¹⁸F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and detected elevated [¹⁸F]PI-2620 PET signals in the presence of high levels of neuronal tau. An innovative approach involving cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons than in the astrocytes of PS19 mice. Regional [¹⁸F]PI-2620 tau PET signals during the lifetime correlated with the abundance of fibrillary tau and with autoradiography signal intensity in PSP patients and disease controls who underwent autopsy 2–63 months after tau PET. In autoradiography, tau-positive neurons and oligodendrocytes with a high AT8 density, but not tau-positive astrocytes, were the drivers of [¹⁸F]PI-2620 autoradiography signals in individuals with PSP. The high tau abundance in oligodendrocytes at the boundary of gray and white matter facilitated the identification of an optimized frontal lobe target region to detect the tau burden in patients with PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau PET radiotracer binding in 4-repeat-tauopathies, translating to an in vivo signal.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02834-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692025","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":"Genome-wide methylation profiling differentiates benign from aggressive and metastatic pituitary neuroendocrine tumors","authors":"Jelena Jotanovic,&nbsp;Henning Bünsow Boldt,&nbsp;Mark Burton,&nbsp;Marianne Skovsager Andersen,&nbsp;Daniel Bengtsson,&nbsp;Thomas Olsson Bontell,&nbsp;Bertil Ekman,&nbsp;Britt Edén Engström,&nbsp;Ulla Feldt-Rasmussen,&nbsp;Ansgar Heck,&nbsp;Antonia Jakovcevic,&nbsp;Jens Otto L. Jørgensen,&nbsp;Ivana Kraljevic,&nbsp;Jacek Kunicki,&nbsp;John R. Lindsay,&nbsp;Marco Losa,&nbsp;Paul Benjamin Loughrey,&nbsp;Dominique Maiter,&nbsp;Maria Maksymowicz,&nbsp;Emilija Manojlovic-Gacic,&nbsp;Jens Pahnke,&nbsp;Stephan Petersenn,&nbsp;Maria Petersson,&nbsp;Vera Popovic,&nbsp;Oskar Ragnarsson,&nbsp;Åse Krogh Rasmussen,&nbsp;Zita Reisz,&nbsp;Wolfgang Saeger,&nbsp;Camilla Schalin-Jäntti,&nbsp;David Scheie,&nbsp;Maria Rosa Terreni,&nbsp;Olli Tynninen,&nbsp;Ben Whitelaw,&nbsp;Pia Burman,&nbsp;Olivera Casar-Borota","doi":"10.1007/s00401-024-02836-5","DOIUrl":"10.1007/s00401-024-02836-5","url":null,"abstract":"<div><p>Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0–2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02836-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142691856","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":"Unsuccessful transmissions of atypical genetic Creutzfeldt–Jakob disease (PRNP p.T183A-129M) in transgenic mice","authors":"Simone Baiardi,&nbsp;Claudia Marina Vargiu,&nbsp;Shirou Mohri,&nbsp;Otto Windl,&nbsp;Jochen Herms,&nbsp;Sabina Capellari,&nbsp;Tetsuyuki Kitamoto,&nbsp;Piero Parchi","doi":"10.1007/s00401-024-02825-8","DOIUrl":"10.1007/s00401-024-02825-8","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142672519","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":"Pure LATE-NC: Frequency, clinical impact, and the importance of considering APOE genotype when assessing this and other subtypes of non-Alzheimer’s pathologies","authors":"Yuriko Katsumata,&nbsp;Xian Wu,&nbsp;Khine Zin Aung,&nbsp;David W. Fardo,&nbsp;Davis C. Woodworth,&nbsp;S. Ahmad Sajjadi,&nbsp;Sandra O. Tomé,&nbsp;Dietmar Rudolf Thal,&nbsp;Juan C. Troncoso,&nbsp;Koping Chang,&nbsp;Charles Mock,&nbsp;Peter T. Nelson","doi":"10.1007/s00401-024-02821-y","DOIUrl":"10.1007/s00401-024-02821-y","url":null,"abstract":"<div><p>Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer’s disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer’s Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses. For &gt; 90% of these participants, apolipoprotein E (<i>APOE)</i> allele status was known; 46.5% had at least one <i>APOE</i> 4 allele. In most human populations, only 15–25% of people are <i>APOE</i> ε4 carriers. ADRCs with higher documented AD risk allele (<i>APOE</i> or <i>BIN1</i>) rates had fewer participants lacking ADNC, and correspondingly low rates of pure LATE-NC. Among <i>APOE</i> ε4 non-carries, 5.3% had pure LATE-NC, 37.0% had pure ADNC, and 3.6% had pure neocortical Lewy body pathology. In terms of clinical impact, participants with pure LATE-NC tended to die after having received a diagnosis of dementia: 56% died with dementia among <i>APOE</i> ε4 non-carrier participants, comparable to 61% with pure ADNC. LATE-NC was associated with increased Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores, i.e. worsened global cognitive impairments, in participants with no/low ADNC and no neocortical Lewy body pathology (p = 0.0023). Among pure LATE-NC cases, there was a trend for higher LATE-NC stages to be associated with worse CDR-SOB scores (p = 0.026 for linear trend of LATE-NC stages). Pure LATE-NC was not associated with clinical features of disinhibition or primary progressive aphasia. In summary, LATE-NC with no or low levels of ADNC was less frequent than pure ADNC but was not rare, particularly among individuals who lacked the <i>APOE</i> 4 allele, and in study cohorts with <i>APOE</i> 4 frequencies similar to those in most human populations.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02821-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637182","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":"Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia","authors":"Charles Arber,&nbsp;Jackie M. Casey,&nbsp;Samuel Crawford,&nbsp;Naiomi Rambarack,&nbsp;Umran Yaman,&nbsp;Sarah Wiethoff,&nbsp;Emma Augustin,&nbsp;Thomas M. Piers,&nbsp;Matthew Price,&nbsp;Agueda Rostagno,&nbsp;Jorge Ghiso,&nbsp;Patrick A. Lewis,&nbsp;Tamas Revesz,&nbsp;John Hardy,&nbsp;Jennifer M. Pocock,&nbsp;Henry Houlden,&nbsp;Jonathan M. Schott,&nbsp;Dervis A. Salih,&nbsp;Tammaryn Lashley,&nbsp;Selina Wray","doi":"10.1007/s00401-024-02820-z","DOIUrl":"10.1007/s00401-024-02820-z","url":null,"abstract":"<div><p>Mutations in <i>ITM2B</i> cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the <i>ITM2B</i> gene (also known as <i>BRI2</i>) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer’s disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of <i>ITM2B/BRI2</i> is 34-fold higher in microglia than neurons and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. The ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. The pathological examination of post-mortem tissue supports the presence of ABri in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. These data have implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer’s disease.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02820-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636668","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":"Correction: Multiciliated ependymal cells: an update on biology and pathology in the adult brain","authors":"Adam M. R. Groh,&nbsp;Yeji Lori Song,&nbsp;Fiona Tea,&nbsp;Brianna Lu,&nbsp;Stephanie Huynh,&nbsp;Elia Afanasiev,&nbsp;Maxime Bigotte,&nbsp;Marc R. Del Bigio,&nbsp;Jo Anne Stratton","doi":"10.1007/s00401-024-02826-7","DOIUrl":"10.1007/s00401-024-02826-7","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611885","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":"The microglial translocator protein (TSPO) in Alzheimer’s disease reflects a phagocytic phenotype","authors":"Emma F. Garland,&nbsp;Henrike Antony,&nbsp;Laura Kulagowska,&nbsp;Thomas Scott,&nbsp;Charlotte Rogien,&nbsp;Michel Bottlaender,&nbsp;James A. R. Nicoll,&nbsp;Delphine Boche","doi":"10.1007/s00401-024-02822-x","DOIUrl":"10.1007/s00401-024-02822-x","url":null,"abstract":"<div><p>Translocator protein (TSPO) is a mitochondrial protein expressed by microglia, ligands for which are used as a marker of neuroinflammation in PET studies of Alzheimer’s disease (AD). We previously showed increasing TSPO load in the cerebral cortex with AD progression, consistent with TSPO PET scan findings. Here, we aim to characterise the microglial phenotype associated with TSPO expression to aid interpretation of the signal generated by TSPO ligands in patients. Human post-mortem sections of temporal lobe (TL) and cerebellum (Cb) from cases classified by Braak group (0–II, III–IV, V–VI; each <i>n</i> = 10) were fluorescently double labelled for TSPO and microglial markers: Iba1, HLA-DR, CD68, MSR-A and CD64. Quantification was performed on scanned images using QuPath software to assess the microglial phenotype of TSPO. Qualitative analysis was also performed for TSPO with GFAP (astrocytes), CD31 (endothelial cells) and CD163 (perivascular macrophages) to characterise the cellular profile of TSPO. The percentage of CD68⁺TSPO⁺ double-labelled cells was significantly higher than for other microglial markers in both brain regions and in all Braak stages, followed by MSR-A⁺TSPO⁺ microglia. Iba1⁺TSPO⁺ cells were more numerous in the cerebellum than the temporal lobe, while CD64⁺TSPO⁺ cells were more numerous in the temporal lobe. No differences were observed for the other microglial markers. TSPO expression was also detected in endothelial cells, but not detected in astrocytes nor in perivascular macrophages. Our data suggest that TSPO is mainly related to a phagocytic profile of microglia (CD68⁺) in human AD, potentially highlighting the ongoing neurodegeneration.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02822-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610349","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":"No sex difference in the extent of acute mechanical blood–brain barrier disruption after experimental concussion","authors":"Hailong Song,&nbsp;Eashwar Kantemneni,&nbsp;Yue Qiu,&nbsp;Jean-Pierre Dolle,&nbsp;D. Kacy Cullen,&nbsp;William Stewart,&nbsp;Douglas H. Smith","doi":"10.1007/s00401-024-02829-4","DOIUrl":"10.1007/s00401-024-02829-4","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611886","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":"Compartment-specific small non-coding RNA changes and nucleolar defects in human mesial temporal lobe epilepsy","authors":"Vamshidhar R. Vangoor,&nbsp;Giuliano Giuliani,&nbsp;Marina de Wit,&nbsp;Carolina K. Rangel,&nbsp;Morten T. Venø,&nbsp;Joran T. Schulte,&nbsp;Andreia Gomes-Duarte,&nbsp;Ketharini Senthilkumar,&nbsp;Noora Puhakka,&nbsp;Jørgen Kjems,&nbsp;Pierre N. E. de Graan,&nbsp;R. Jeroen Pasterkamp","doi":"10.1007/s00401-024-02817-8","DOIUrl":"10.1007/s00401-024-02817-8","url":null,"abstract":"<div><p>Mesial temporal lobe epilepsy (mTLE) is a debilitating disease characterized by recurrent seizures originating from temporal lobe structures such as the hippocampus. The pathogenic mechanisms underlying mTLE are incompletely understood but include changes in the expression of non-coding RNAs in affected brain regions. Previous work indicates that some of these changes may be selective to specific sub-cellular compartments, but the full extent of these changes and how these sub-cellular compartments themselves are affected remains largely unknown. Here, we performed small RNA sequencing (RNA-seq) of sub-cellular fractions of hippocampal tissue from mTLE patients and controls to determine nuclear and cytoplasmic expression levels of microRNAs (miRNAs). This showed differential expression of miRNAs and isomiRs, several of which displayed enriched nuclear expression in mTLE. Subsequent analysis of <i>miR-92b</i>, the most strongly deregulated miRNA in the nucleus, showed accumulation of this miRNA in the nucleolus in mTLE and association with snoRNAs. This prompted us to further study the nucleolus in human mTLE which uncovered several defects, such as altered nucleolar size or shape, mis-localization of nucleolar proteins, and deregulation of snoRNAs, indicative of nucleolar stress. In a rat model of epilepsy, nucleolar phenotypes were detected in the latency period before the onset of spontaneous seizures, suggesting that nucleolar changes may contribute to the development of seizures and mTLE. Overall, these data for the first time implicate nucleolar defects in the pathogenesis of mTLE and provide a valuable framework for further defining the functional consequences of altered sub-cellular RNA profiles in this disease.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02817-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594914","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":"TMEM106B amyloid filaments in the Biondi bodies of ependymal cells","authors":"Bernardino Ghetti,&nbsp;Manuel Schweighauser,&nbsp;Max H. Jacobsen,&nbsp;Derrick Gray,&nbsp;Mehtap Bacioglu,&nbsp;Alexey G. Murzin,&nbsp;Bradley S. Glazier,&nbsp;Taxiarchis Katsinelos,&nbsp;Ruben Vidal,&nbsp;Kathy L. Newell,&nbsp;Sujuan Gao,&nbsp;Holly J. Garringer,&nbsp;Maria Grazia Spillantini,&nbsp;Sjors H. W. Scheres,&nbsp;Michel Goedert","doi":"10.1007/s00401-024-02807-w","DOIUrl":"10.1007/s00401-024-02807-w","url":null,"abstract":"<div><p>Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer’s disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02807-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581839","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}