Acta Neuropathologica Communications最新文献

{"title":"Correction to: Alzheimer's disease tau is a prominent pathology in LRRK2 Parkinson's disease.","authors":"Michael X Henderson, Medha Sengupta, John Q Trojanowski, Virginia M Y Lee","doi":"10.1186/s40478-024-01819-7","DOIUrl":"10.1186/s40478-024-01819-7","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"110"},"PeriodicalIF":6.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465347","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":"Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia.","authors":"Diana Wiesner, Simone Feldengut, Sarah Woelfle, Tobias M Boeckers, Albert C Ludolph, Francesco Roselli, Kelly Del Tredici","doi":"10.1186/s40478-024-01792-1","DOIUrl":"10.1186/s40478-024-01792-1","url":null,"abstract":"<p><p>We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer's disease (AD, n = 8), Pick's disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"108"},"PeriodicalIF":6.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465348","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":"Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial.","authors":"Oana M Dumitrascu, Jonah Doustar, Dieu-Trang Fuchs, Yosef Koronyo, Dale S Sherman, Michelle Shizu Miller, Kenneth O Johnson, Roxana O Carare, Steven R Verdooner, Patrick D Lyden, Julie A Schneider, Keith L Black, Maya Koronyo-Hamaoui","doi":"10.1186/s40478-024-01810-2","DOIUrl":"10.1186/s40478-024-01810-2","url":null,"abstract":"<p><p>The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"109"},"PeriodicalIF":6.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465350","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":"Atrx loss as a promising screening tool for the identification of diffuse midline glioma subtype, H3K27/MAPKinase co-altered.","authors":"Arnault Tauziède-Espariat, David Castel, Yassine Ajlil, Lucie Auffret, Romain Appay, Cassandra Mariet, Lauren Hasty, Alice Métais, Fabrice Chrétien, Jacques Grill, Pascale Varlet","doi":"10.1186/s40478-024-01818-8","DOIUrl":"10.1186/s40478-024-01818-8","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"105"},"PeriodicalIF":6.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454545","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":"Publisher Correction: Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor‑like population.","authors":"Joshua A Regal, María E Guerra García, Vaibhav Jain, Vidyalakshmi Chandramohan, David M Ashley, Simon G Gregory, Eric M Thompson, Giselle Y López, Zachary J Reitman","doi":"10.1186/s40478-024-01788-x","DOIUrl":"https://doi.org/10.1186/s40478-024-01788-x","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"107"},"PeriodicalIF":6.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465349","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":"Pediatric central nervous system tumor with CIC::LEUTX fusion: a diagnostic challenge.","authors":"Yanghao Hou, Yanru Du, Juan Wang, Xinke Zhang, Xueyan Zhao, Xinyi Xian, Li Yuan, Haigang Li, Yu Wang, Shaoyan Xi, Guan Huang, Wenbiao Zhu, Juan Wang, Jin Zhu, Qiubo Yu, Youde Cao, JingXian Wu, Jing Zeng, Gehong Dong, Wanming Hu","doi":"10.1186/s40478-024-01824-w","DOIUrl":"10.1186/s40478-024-01824-w","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"106"},"PeriodicalIF":6.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454547","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":"Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC), new name and new problems: an illustration of one case with atypical morphology and biology.","authors":"Arnault Tauziède-Espariat, Lelio Guida, Volodia Dangouloff-Ros, Nathalie Boddaert, Gaëlle Pierron, Delphine Guillemot, Julien Masliah-Planchon, Lauren Hasty, Alice Métais, Fabrice Chrétien, Pascale Varlet","doi":"10.1186/s40478-024-01822-y","DOIUrl":"10.1186/s40478-024-01822-y","url":null,"abstract":"<p><p>A novel histomolecular tumor of the central nervous system (CNS), the \"diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC),\" has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"104"},"PeriodicalIF":6.2,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11201364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454546","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":"Altered brain expression and cerebrospinal fluid levels of TIMP4 in cerebral amyloid angiopathy.","authors":"Lieke Jäkel, Anna M De Kort, Arno Stellingwerf, Carla Hernández Utrilla, Iris Kersten, Marc Vervuurt, Yannick Vermeiren, Benno Küsters, Floris H B M Schreuder, Catharina J M Klijn, H Bea Kuiperij, Marcel M Verbeek","doi":"10.1186/s40478-024-01823-x","DOIUrl":"10.1186/s40478-024-01823-x","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy (CAA) is a highly prevalent and progressive pathology, involving amyloid-β (Aβ) deposition in the cerebral blood vessel walls. CAA is associated with an increased risk for intracerebral hemorrhages (ICH). Insight into the molecular mechanisms associated with CAA pathology is urgently needed, to develop additional diagnostic tools to allow for reliable and early diagnosis of CAA and to obtain novel leads for the development of targeted therapies. Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) is associated with cardiovascular functioning and disease and has been linked to vascular dementia. Using immunohistochemistry, we studied occipital brain tissue samples of 57 patients with CAA (39 without ICH and 18 with ICH) and 42 controls, and semi-quantitatively assessed expression levels of TIMP4. Patients with CAA had increased vascular expression of TIMP4 compared to controls (p < 0.001), and in these patients, TIMP4 expression correlated with CAA severity (τ_b = 0.38; p = 0.001). Moreover, TIMP4 expression was higher in CAA-ICH compared to CAA-non-ICH cases (p = 0.024). In a prospective cross-sectional study of 38 patients with CAA and 37 age- and sex-matched controls, we measured TIMP4 levels in cerebrospinal fluid (CSF) and serum using ELISA. Mean CSF levels of TIMP4 were decreased in patients with CAA compared to controls (3.36 ± 0.20 vs. 3.96 ± 0.22 ng/ml, p = 0.033), whereas median serum levels were increased in patients with CAA (4.51 ng/ml [IQR 3.75-5.29] vs 3.60 ng/ml [IQR 3.11-4.85], p-9.013). Moreover, mean CSF TIMP4 levels were lower in CAA patients who had experienced a symptomatic hemorrhage compared to CAA patients who did not (2.13 ± 0.24 vs. 3.57 ± 0.24 ng/ml, p = 0.007). CSF TIMP4 levels were associated with CSF levels of Aβ40 (spearman r (r_s) = 0.321, p = 0.009). In summary, we show that TIMP4 is highly associated with CAA and CAA-related ICH, which is reflected by higher levels in the cerebral vasculature and lower levels in CSF. With these findings we provide novel insights into the pathophysiology of CAA, and more specifically in CAA-associated ICH.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"103"},"PeriodicalIF":6.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445221","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":"snRNA-seq of human cutaneous neurofibromas before and after selumetinib treatment implicates role of altered Schwann cell states, inter-cellular signaling, and extracellular matrix in treatment response.","authors":"Cameron Church, Christian X Fay, Emil Kriukov, Hui Liu, Ashley Cannon, Lauren Ashley Baldwin, David K Crossman, Bruce Korf, Margaret R Wallace, Andrea M Gross, Brigitte C Widemann, Robert A Kesterson, Petr Baranov, Deeann Wallis","doi":"10.1186/s40478-024-01821-z","DOIUrl":"10.1186/s40478-024-01821-z","url":null,"abstract":"<p><p>Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor. The purpose of this study was to analyze the transcriptome of cNF tumors before and on selumetinib treatment to understand both tumor composition and response. We obtained biopsy sets of tumors both pre- and on- selumetinib treatment from the same individuals and were able to collect sets from four separate individuals. We sequenced mRNA from 5844 nuclei and identified 30,442 genes in the untreated group and sequenced 5701 nuclei and identified 30,127 genes in the selumetinib treated group. We identified and quantified distinct populations of cells (Schwann cells, fibroblasts, pericytes, myeloid cells, melanocytes, keratinocytes, and two populations of endothelial cells). While we anticipated that cell proportions might change with treatment, we did not identify any one cell population that changed significantly, likely due to an inherent level of variability between tumors. We also evaluated differential gene expression based on drug treatment in each cell type. Ingenuity pathway analysis (IPA) was also used to identify pathways that differ on treatment. As anticipated, we identified a significant decrease in ERK/MAPK signaling in cells including Schwann cells but most specifically in myeloid cells. Interestingly, there is a significant decrease in opioid signaling in myeloid and endothelial cells; this downward trend is also observed in Schwann cells and fibroblasts. Cell communication was assessed by RNA velocity, Scriabin, and CellChat analyses which indicated that Schwann cells and fibroblasts have dramatically altered cell states defined by specific gene expression signatures following treatment (RNA velocity). There are dramatic changes in receptor-ligand pairs following treatment (Scriabin), and robust intercellular signaling between virtually all cell types associated with extracellular matrix (ECM) pathways (Collagen, Laminin, Fibronectin, and Nectin) is downregulated after treatment. These response specific gene signatures and interaction pathways could provide clues for understanding treatment outcomes or inform future therapies.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"102"},"PeriodicalIF":6.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436544","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 multi-institutional series of a novel, recurrent TRIM24::MET fusion-driven infant-type hemispheric glioma reveals significant clinico-pathological heterogeneity.","authors":"David Gorodezki, Jason Chiang, Angela N Viaene, Philipp Sievers, Simone Schmid, Ursula Holzer, Frank Paulsen, Martin U Schuhmann, Olaf Witt, Jens Schittenhelm, Martin Ebinger","doi":"10.1186/s40478-024-01817-9","DOIUrl":"10.1186/s40478-024-01817-9","url":null,"abstract":"<p><p>Within the past decade, incremental integration of molecular characteristics into the classification of central nervous system neoplasms increasingly facilitated precise diagnosis and advanced stratification, beyond potentially providing the foundation for advanced targeted therapies. We report a series of three cases of infant-type hemispheric glioma (IHG) involving three infants diagnosed with neuroepithelial tumors of the cerebral hemispheres harboring a novel, recurrent TRIM24::MET fusion. Histopathology showed glial tumors with either low-grade or high-grade characteristics, while molecular characterization found an additional homozygous CDKN2A/B deletion in two cases. Two patients showed leptomeningeal dissemination, while multiple supra- and infratentorial tumor manifestations were found in one case. Following subtotal resection (two cases) and biopsy (one case), treatment intensity of adjuvant chemotherapy regimens did not reflect in the progression patterns within the reported cases. Two patients showed progression after first-line treatment, of which one patient died not responding to tyrosine kinase inhibitor cabozantinib. As the detection of a recurrent TRIM24::MET fusion expands the spectrum of renowned driving fusion genes in IHG, this comparative illustration may indicate a distinct clinico-pathological heterogeneity of tumors bearing this driver alteration. Upfront clinical trials of IHG promoting further characterization and the implementation of individualized therapies involving receptor tyrosine kinase inhibition are required.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"101"},"PeriodicalIF":6.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431076","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}