Acta Neuropathologica Communications最新文献

{"title":"Correction to: Interplay between androgen and CXCR4 chemokine signaling in myelin repair.","authors":"Narimene Asbelaoui, Charly Abi-Ghanem, Geraldine Schlecht-Louf, Hania Oukil, Cindy Degerny, The Netherlands Brain Bank, Michael Schumacher, Abdel Mouman Ghoumarir","doi":"10.1186/s40478-024-01774-3","DOIUrl":"10.1186/s40478-024-01774-3","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"116"},"PeriodicalIF":6.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618947","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":"Correction: Tau seed amplification assay reveals relationship between seeding and pathological forms of tau in Alzheimer's disease brain.","authors":"Bryan Frey, David Holzinger, Keenan Taylor, Dagmar E Ehrnhoefer, Andreas Striebinger, Sandra Biesinger, Laura Gasparini, Michael J O'Neill, Florian Wegner, Stefan Barghorn, Günter U Höglinger, Roland G Heym","doi":"10.1186/s40478-024-01825-9","DOIUrl":"10.1186/s40478-024-01825-9","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"115"},"PeriodicalIF":6.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615608","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":"Early biomarkers in the presymptomatic phase of cognitive impairment: changes in the endocannabinoidome and serotonergic pathways in Alzheimer's-prone mice after mTBI.","authors":"Francesca Guida, Monica Iannotta, Anna Lauritano, Rosmara Infantino, Emanuela Salviati, Roberta Verde, Livio Luongo, Eduardo Maria Sommella, Fabio Arturo Iannotti, Pietro Campiglia, Sabatino Maione, Vincenzo Di Marzo, Fabiana Piscitelli","doi":"10.1186/s40478-024-01820-0","DOIUrl":"10.1186/s40478-024-01820-0","url":null,"abstract":"<p><strong>Background: </strong>Despite extensive studies on the neurobiological correlates of traumatic brain injury (TBI), little is known about its molecular determinants on long-term consequences, such as dementia and Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Here, we carried out behavioural studies and an extensive biomolecular analysis, including inflammatory cytokines, gene expression and the combination of LC-HRMS and MALDI-MS Imaging to elucidate the targeted metabolomics and lipidomics spatiotemporal alterations of brains from wild-type and APP-SWE mice, a genetic model of AD, at the presymptomatic stage, subjected to mild TBI.</p><p><strong>Results: </strong>We found that brain injury does not affect cognitive performance in APP-SWE mice. However, we detected an increase of key hallmarks of AD, including Aβ_1-42 levels and BACE1 expression, in the cortices of traumatized transgenic mice. Moreover, significant changes in the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), occurred, including increased levels of the endocannabinoid 2-AG in APP-SWE mice in both the cortex and hippocampus, and N-acylserotonins, detected for the first time in the brain. The gene expression of enzymes for the biosynthesis and inactivation of eCBs and eCB-like mediators, and some of their main molecular targets, also underwent significant changes. We also identified the formation of heteromers between cannabinoid 1 (CB₁) and serotonergic 2A (5HT_2A) receptors, whose levels increased in the cortex of APP-SWE mTBI mice, possibly contributing to the exacerbated pathophysiology of AD induced by the trauma.</p><p><strong>Conclusions: </strong>Mild TBI induces biochemical changes in AD genetically predisposed mice and the eCBome may play a role in the pathogenetic link between brain injury and neurodegenerative disorders also by interacting with the serotonergic system.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"113"},"PeriodicalIF":6.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589384","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 pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC.","authors":"Ryan K Shahidehpour, Peter T Nelson, Adam D Bachstetter","doi":"10.1186/s40478-024-01826-8","DOIUrl":"10.1186/s40478-024-01826-8","url":null,"abstract":"<p><strong>Background: </strong>TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as \"Lin bodies,\" located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for astrocytes, IBA1 for microglia) and ferritin. Analyses were conducted on post-mortem brain tissues collected from individuals with pathologically confirmed Alzheimer's disease neuropathological changes (ADNC) and LATE-NC.</p><p><strong>Results: </strong>As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body-positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity.</p><p><strong>Conclusions: </strong>Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"114"},"PeriodicalIF":6.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598091","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":"Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.","authors":"E Keats Shwab, Daniel C Gingerich, Zhaohui Man, Julia Gamache, Melanie E Garrett, Gregory E Crawford, Allison E Ashley-Koch, Geidy E Serrano, Thomas G Beach, Michael W Lutz, Ornit Chiba-Falek","doi":"10.1186/s40478-024-01803-1","DOIUrl":"10.1186/s40478-024-01803-1","url":null,"abstract":"<p><p>The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"111"},"PeriodicalIF":6.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490460","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":"Correction: Retina-to-brain spreading of α-synuclein after intravitreal injection of preformed fibrils.","authors":"Dayana Pérez-Acuña, Ka Hyun Rhee, Soo Jean Shin, Jeeyun Ahn, Jee-Young Lee, Seung-Jae Lee","doi":"10.1186/s40478-024-01816-w","DOIUrl":"10.1186/s40478-024-01816-w","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"112"},"PeriodicalIF":6.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490459","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":"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}