Acta Neuropathologica最新文献

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

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

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

{"title":"Epigenetic and genetic risk of Alzheimer disease from autopsied brains in two ethnic groups","authors":"Yiyi Ma,&nbsp;Dolly Reyes-Dumeyer,&nbsp;Angel Piriz,&nbsp;Patricia Recio,&nbsp;Diones Rivera Mejia,&nbsp;Martin Medrano,&nbsp;Rafael A. Lantigua,&nbsp;Jean Paul G. Vonsattel,&nbsp;Giuseppe Tosto,&nbsp;Andrew F. Teich,&nbsp;Benjamin Ciener,&nbsp;Sandra Leskinen,&nbsp;Sharanya Sivakumar,&nbsp;Michael DeTure,&nbsp;Duara Ranjan,&nbsp;Dennis Dickson,&nbsp;Melissa Murray,&nbsp;Edward Lee,&nbsp;David A. Wolk,&nbsp;Lee-Way Jin,&nbsp;Brittany N. Dugger,&nbsp;Annie Hiniker,&nbsp;Robert A. Rissman,&nbsp;Richard Mayeux,&nbsp;Badri N. Vardarajan","doi":"10.1007/s00401-024-02778-y","DOIUrl":"10.1007/s00401-024-02778-y","url":null,"abstract":"<div><p> Genetic variants and epigenetic features both contribute to the risk of Alzheimer’s disease (AD). We studied the AD association of CpG-related single nucleotide polymorphisms (CGS), which act as a hub of both the genetic and epigenetic effects, in Caribbean Hispanics (CH) and generalized the findings to Non-Hispanic Whites (NHW). First, we conducted a genome-wide, sliding-window-based association with AD, in 7,155 CH and 1,283 NHW participants. Next, using data from the dorsolateral prefrontal cortex in 179 CH brains, we tested the cis- and trans-effects of AD-associated CGS on brain DNA methylation to mRNA expression. For the genes with significant cis- and trans-effects, we investigated their enriched pathways. We identified six genetic loci in CH with CGS dosage associated with AD at genome-wide significance levels: <i>ADAM20</i> (Score = 55.19, <i>P</i> = 4.06 × 10^–8), the intergenic region between <i>VRTN</i> and <i>SYNDIG1L</i> (Score = − 37.67, <i>P</i> = 2.25 × 10^–9), <i>SPG7</i> (16q24.3) (Score = 40.51, <i>P</i> = 2.23 × 10^–8), <i>PVRL2</i> (Score = 125.86, <i>P</i> = 1.64 × 10^–9), <i>TOMM40</i> (Score = − 18.58, <i>P</i> = 4.61 × 10^–8), and <i>APOE</i> (Score = 75.12, <i>P</i> = 7.26 × 10^–26). CGSes in <i>PVRL2</i> and <i>APOE</i> were also significant in NHW. Except for <i>ADAM20</i>, CGSes in the other five loci were associated with CH brain methylation levels (mQTLs) and CGSes in <i>SPG7, PVRL2,</i> and <i>APOE</i> were also mQTLs in NHW. Except for <i>SYNDIG1L</i> (<i>P</i> = 0.08), brain methylation levels in the other five loci affected downstream mRNA expression in CH (<i>P</i> &lt; 0.05), and methylation at <i>VRTN</i> and <i>TOMM40</i> were also associated with mRNA expression in NHW. Gene expression in these six loci were also regulated by CpG sites in genes that were enriched in the neuron projection and glutamatergic synapse pathways (FDR &lt; 0.05). DNA methylation at all six loci and mRNA expression of <i>SYNDIG1</i> and <i>TOMM40</i> were significantly associated with Braak Stage in CH. In summary, we identified six CpG-related genetic loci associated with AD in CH, harboring both genetic and epigenetic risks. However, their downstream effects on mRNA expression maybe ethnic specific and different from NHW.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034912","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":"FGFR1 wild-type rosette-forming glioneuronal tumours","authors":"Mégane Le Quang,&nbsp;Aude Trinquet,&nbsp;Aurore Siegfried,&nbsp;Amaury de Barros,&nbsp;Luc Bauchet,&nbsp;Sam Ng,&nbsp;Vincent Jecko,&nbsp;Guillaume Chotard,&nbsp;Morgan Ollivier,&nbsp;Gilles Adam,&nbsp;Fabrice Bonneville,&nbsp;Julien Masliah-Planchon,&nbsp;Yvan Nicaise,&nbsp;Clémentine Decamps,&nbsp;Valérie Rigau,&nbsp;Emmanuelle Uro-Coste","doi":"10.1007/s00401-024-02779-x","DOIUrl":"10.1007/s00401-024-02779-x","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02779-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013840","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":"Severe neurodegeneration in brains of transgenic rats producing human tau prions","authors":"Jacob Ayers,&nbsp;T. Peter Lopez,&nbsp;Ian T. Steele,&nbsp;Abby Oehler,&nbsp;Rigo Roman-Albarran,&nbsp;Elisa Cleveland,&nbsp;Alex Chong,&nbsp;George A. Carlson,&nbsp;Carlo Condello,&nbsp;Stanley B. Prusiner","doi":"10.1007/s00401-024-02771-5","DOIUrl":"10.1007/s00401-024-02771-5","url":null,"abstract":"<div><p>Both wild-type and mutant tau proteins can misfold into prions and self-propagate in the central nervous system of animals and people. To extend the work of others, we investigated the molecular basis of tau prion–mediated neurodegeneration in transgenic (Tg) rats expressing mutant human tau (P301S); this line of Tg rats is denoted Tg12099. We used the rat <i>Prnp</i> promoter to drive the overexpression of mutant tau (P301S) in the human 0N4R isoform. In Tg12099(+/+) rats homozygous for the transgene, ubiquitous expression of mutant human tau resulted in the progressive accumulation of phosphorylated tau inclusions, including silver-positive tangles in the frontal cortices and limbic system. Signs of central nervous system dysfunction were found in terminal Tg12099(+/+) rats exhibiting severe neurodegeneration and profound atrophy of the amygdala and piriform cortex. The greatest increases in tau prion activity were found in the corticolimbic structures. In contrast to the homozygous Tg12099(+/+) rats, we found lower levels of mutant tau in the hemizygous rats, resulting in few neuropathologic changes up to 2 years of age. Notably, these hemizygous rats could be infected by intracerebral inoculation with recombinant tau fibrils or precipitated tau prions from the brain homogenates of sick, aged homozygous Tg12099(+/+) rats. Our studies argue that the regional propagation of tau prions and neurodegeneration in the Tg12099 rats resembles that found in human primary tauopathies. These findings seem likely to advance our understanding of human tauopathies and may lead to effective therapeutics for Alzheimer’s disease and other tau prion disorders.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003326","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":"Neuropathological hallmarks in the post-mortem retina of neurodegenerative diseases","authors":"Frederique J. Hart de Ruyter,&nbsp;Manon J. A. P. Evers,&nbsp;Tjado H. J. Morrema,&nbsp;Anke A. Dijkstra,&nbsp;Jurre den Haan,&nbsp;Jos W. R. Twisk,&nbsp;Johannes F. de Boer,&nbsp;Philip Scheltens,&nbsp;Femke H. Bouwman,&nbsp;Frank D. Verbraak,&nbsp;Annemieke J. Rozemuller,&nbsp;Jeroen J. M. Hoozemans","doi":"10.1007/s00401-024-02769-z","DOIUrl":"10.1007/s00401-024-02769-z","url":null,"abstract":"&lt;div&gt;&lt;p&gt;The retina is increasingly recognised as a potential source of biomarkers for neurodegenerative diseases. Hallmark protein aggregates in the retinal neuronal tissue could be imaged through light non-invasively. Post-mortem studies have already shown the presence of specific hallmark proteins in Alzheimer’s disease, primary tauopathies, synucleinopathies and frontotemporal lobar degeneration. This study aims to assess proteinopathy in a post-mortem cohort with different neurodegenerative diseases and assess the presence of the primary pathology in the retina. Post-mortem eyes were collected in collaboration with the Netherlands Brain Bank from donors with Alzheimer’s disease (&lt;i&gt;n&lt;/i&gt; = 17), primary tauopathies (&lt;i&gt;n&lt;/i&gt; = 8), synucleinopathies (&lt;i&gt;n&lt;/i&gt; = 27), frontotemporal lobar degeneration (&lt;i&gt;n&lt;/i&gt; = 8), mixed pathology (&lt;i&gt;n&lt;/i&gt; = 11), other neurodegenerative diseases (&lt;i&gt;n&lt;/i&gt; = 6), and cognitively normal controls (&lt;i&gt;n&lt;/i&gt; = 25). Multiple cross sections of the retina and optic nerve tissue were immunostained using antibodies against pTau Ser202/Thr205 (AT8), amyloid-beta (4G8), alpha-synuclein (LB509), pTDP-43 Ser409/410 and p62-lck ligand (p62) and were assessed for the presence of aggregates and inclusions. pTau pathology was observed as a diffuse signal in Alzheimer’s disease, primary tauopathies and controls with Alzheimer’s disease neuropathological changes. Amyloid-beta was observed in the vessel wall and as cytoplasmic granular deposits in all groups. Alpha-synuclein pathology was observed as Lewy neurites in the retina in synucleinopathies associated with Lewy pathology and as oligodendroglial cytoplasmic inclusions in the optic nerve in multiple system atrophy. Anti-pTDP-43 generally showed typical neuronal cytoplasmic inclusion bodies in cases with frontotemporal lobar degeneration with TDP-43 and also in cases with later stages of limbic-associated TDP-43 encephalopathy. P62 showed inclusion bodies similar to those seen with anti-pTDP-43. Furthermore, pTau and alpha-synuclein pathology were significantly associated with increasing Braak stages for neurofibrillary tangles and Lewy bodies, respectively. Mixed pathology cases in this cohort consisted of cases (&lt;i&gt;n&lt;/i&gt; = 6) with high Braak LB stages (&gt; 4) and low or moderate AD pathology, high AD pathology (&lt;i&gt;n&lt;/i&gt; = 1, Braak NFT 6, Thal phase 5) with moderate LB pathology, or a combination of low/moderate scores for different pathology scores in the brain (&lt;i&gt;n&lt;/i&gt; = 4). There were no cases with advanced co-pathologies. In seven cases with Braak LB ≥ 4, LB pathology was observed in the retina, while tau pathology in the retina in the mixed pathology group (&lt;i&gt;n&lt;/i&gt; = 11) could not be observed. From this study, we conclude that the retina reflects the presence of the major hallmark proteins associated with neurodegenerative diseases. Although low or moderate levels of copathology were found in the brains of most cases, the retina primarily manifested protein aggregates","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003325","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 polyG-dependent neurodegeneration in neuronal intranuclear inclusion disease","authors":"Shaoping Zhong,&nbsp;Yangye Lian,&nbsp;Binbin Zhou,&nbsp;Ruiqing Ren,&nbsp;Lewei Duan,&nbsp;Yuyin Pan,&nbsp;Yuchen Gong,&nbsp;Xiaoling Wu,&nbsp;Dengfeng Cheng,&nbsp;Puming Zhang,&nbsp;Boxun Lu,&nbsp;Xin Wang,&nbsp;Jing Ding","doi":"10.1007/s00401-024-02776-0","DOIUrl":"10.1007/s00401-024-02776-0","url":null,"abstract":"<div><p>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by the expansion of GGC trinucleotide repeats in <i>NOTCH2NLC</i> gene. Despite identifying uN2CpolyG, a toxic polyglycine (polyG) protein translated by expanded GGC repeats, the exact pathogenic mechanisms of NIID remain unclear. In this study, we investigated the role of polyG by expressing various forms of <i>NOTCH2NLC</i> in mice: the wild-type, the expanded form with 100 GGC repeats (either translating or not translating into uN2CpolyG), and the mutated form that encodes a pure polyG without GGC-repeat RNA and the C-terminal stretch (uN2CpolyG-dCT). Both uN2CpolyG and uN2CpolyG-dCT induced the formation of inclusions composed by filamentous materials and resulted in neurodegenerative phenotypes in mice, including impaired motor and cognitive performance, shortened lifespan, and pathologic lesions such as white-matter lesions, microgliosis, and astrogliosis. In contrast, expressing GGC-repeat RNA alone was non-pathogenic. Through bulk and single-nuclei RNA sequencing, we identified common molecular signatures linked to the expression of uN2CpolyG and uN2CpolyG-dCT, particularly the upregulation of inflammation and microglia markers, and the downregulation of immediate early genes and splicing factors. Importantly, microglia-mediated inflammation was visualized in NIID patients using positron emission tomography, correlating with levels of white-matter atrophy. Furthermore, microglia ablation ameliorated neurodegenerative phenotypes and transcriptional alterations in uN2CpolyG-expressing mice but did not affect polyG inclusions. Together, these results demonstrate that polyG is crucial for the pathogenesis of NIID and highlight the significant role of microglia in polyG-induced neurodegeneration.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02776-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987141","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":"Reply to L. Lucchino et al. on commentary on “Histologic correlates of “Choroidal Abnormalities” in Neurofibromatosis type 1”","authors":"Anat O. Stemmer-Rachamimov,&nbsp;Liana Kozanno,&nbsp;Scott R. Plotkin,&nbsp;Justin T. Jordan,&nbsp;Joseph F. Rizzo 3rd","doi":"10.1007/s00401-024-02782-2","DOIUrl":"10.1007/s00401-024-02782-2","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02782-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987142","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":"Key features of choroidal abnormalities in neurofibromatosis type 1, a commentary on “Histologic correlates of “choroidal abnormalities” in neurofibromatosis type 1 (NF1)”","authors":"Luca Lucchino,&nbsp;Fabiana Mallone,&nbsp;Magda Gharbiya,&nbsp;Ludovico Alisi","doi":"10.1007/s00401-024-02783-1","DOIUrl":"10.1007/s00401-024-02783-1","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"148 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02783-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987180","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}