Acta Neuropathologica最新文献

{"title":"Oligodendroglia vulnerability in the human dorsal striatum in Parkinson’s disease","authors":"Juan M. Barba-Reyes,&nbsp;Lisbeth Harder,&nbsp;Sergio Marco Salas,&nbsp;Methasit Jaisa-aad,&nbsp;Clara Muñoz-Castro,&nbsp;Leonardo D. Garma,&nbsp;Nima Rafati,&nbsp;Mats Nilsson,&nbsp;Bradley T. Hyman,&nbsp;Alberto Serrano-Pozo,&nbsp;Ana B. Muñoz-Manchado","doi":"10.1007/s00401-025-02884-5","DOIUrl":"10.1007/s00401-025-02884-5","url":null,"abstract":"<div><p>Oligodendroglia are the responsible cells for myelination in the central nervous system and their involvement in Parkinson’s disease (PD) is poorly understood. We performed sn-RNA-seq and image-based spatial transcriptomics of human caudate nucleus and putamen (dorsal striatum) from PD and control brain donors to elucidate the diversity of oligodendroglia and how they are affected by the disease. We profiled a total of ~ 200.000 oligodendroglial nuclei, defining 15 subclasses, from precursor to mature cells, 4 of which are disease-associated. These PD-specific populations are characterized by the overexpression of heat shock proteins, as well as distinct expression signatures related to immune responses, myelination alterations, and disrupted cell signaling pathways. We have also identified impairments in cell communication and oligodendrocyte development, evidenced by changes in neurotransmitter receptors expression and cell adhesion molecules. In addition, we observed significant disruptions in oligodendrocyte development, with aberrant differentiation trajectories and shifts in cell proportions, particularly in the transition from mature oligodendrocytes to disease-associated states. Quantitative immunohistochemical analysis revealed decreased myelin levels in the PD striatum, which correlated with transcriptomic alterations. Furthermore, spatial transcriptomics mapping revealed the distinct localization of disease-associated populations within the striatum, with evidence of impaired myelin integrity. Thus, we uncover oligodendroglia as a critical cell type in PD and a potential new therapeutic target for myelin-based interventions.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02884-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908791","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 interactome of tau phosphorylated at T217 in Alzheimer’s disease human brain tissue","authors":"Tomas Kavanagh,&nbsp;Manon Thierry,&nbsp;Kaleah Balcomb,&nbsp;Jackeline Ponce,&nbsp;Evgeny Kanshin,&nbsp;Alexander Tapia-Sealey,&nbsp;Glenda Halliday,&nbsp;Beatrix Ueberheide,&nbsp;Thomas Wisniewski,&nbsp;Eleanor Drummond","doi":"10.1007/s00401-025-02881-8","DOIUrl":"10.1007/s00401-025-02881-8","url":null,"abstract":"<div><p>Hyperphosphorylated tau (pTau) in Alzheimer’s disease (AD) brain tissue is a complex mix of multiple tau species that are variably phosphorylated. The emerging studies suggest that phosphorylation of specific residues may alter the role of tau. The role of specific pTau species can be explored through protein interactome studies. The aim of this study was to analyse the interactome of tau phosphorylated at T217 (pT217), which biomarker studies suggest is one of the earliest accumulating tau species in AD. pT217 interactors were identified in fresh-frozen human brain tissue from 10 cases of advanced AD using affinity purification-mass spectrometry. The cases included a balanced cohort of <i>APOE</i> ε3/ε3 and ε4/ε4 genotypes (<i>n</i> = 5 each) to explore how apolipoprotein E altered phosphorylated tau interactions. The results were compared to our previous interactome dataset that profiled the interactors of PHF1-enriched tau to determine if individual pTau species have different interactomes. 23 proteins were identified as <i>bona fide</i> pT217 interactors, including known pTau interactor SQSTM1. pT217 enriched tau was phosphorylated at fewer residues compared to PHF1-enriched tau, suggesting an earlier stage of pathology development. Notable pT217 interactors included five subunits of the CTLH E3 ubiquitin ligase (WDR26, ARMC8, GID8, RANBP9, MAEA), which has not previously been linked to AD. In <i>APOE</i> ε3/ε3 cases pT217 significantly interacted with 46 proteins compared to 28 in <i>APOE</i> ε4/ε4 cases, but these proteins were significantly overlapped. CTLH E3 ubiquitin ligase subunits significantly interacted with phosphorylated tau in both <i>APOE</i> genotypes. pT217 interactions with SQSTM1, WDR26 and RANBP9 were validated using co-immunoprecipitation and immunofluorescent microscopy of post-mortem human brain tissue, which showed colocalisation of both protein interactors with tau pathology. Our results report the interactome of pT217 in human Alzheimer’s disease brain tissue for the first time and highlight the CTLH E3 ubiquitin ligase complex as a significant novel interactor of pT217 tau.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02881-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900828","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":"DNA methylation identifies body segment origins of spinal ependymomas","authors":"Erika Yamazawa,&nbsp;Shota Tanaka,&nbsp;Genta Nagae,&nbsp;Takayoshi Umeda,&nbsp;Kenji Tatsuno,&nbsp;Taijun Hana,&nbsp;Phyo Kim,&nbsp;Toshihiro Takami,&nbsp;Keisuke Takai,&nbsp;Takashi Komori,&nbsp;Ryohei Otani,&nbsp;Fumi Higuchi,&nbsp;Hirokazu Takami,&nbsp;Keisuke Yamada,&nbsp;Masashi Nomura,&nbsp;Akitake Mukasa,&nbsp;Shunsaku Takayanagi,&nbsp;Hideaki Imai,&nbsp;Hiroyuki Aburatani,&nbsp;Nobuhito Saito","doi":"10.1007/s00401-025-02885-4","DOIUrl":"10.1007/s00401-025-02885-4","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902748","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":"Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases","authors":"Nanna Møller Jensen,&nbsp;Zagorka Vitic,&nbsp;Mia R. Antorini,&nbsp;Tobias Bruun Viftrup,&nbsp;Laura Parkkinen,&nbsp;Poul Henning Jensen","doi":"10.1007/s00401-025-02871-w","DOIUrl":"10.1007/s00401-025-02871-w","url":null,"abstract":"<div><p>Lewy body diseases are common neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies, which lead to both motor and non-motor symptoms. They are neuropathologically characterized by loss of neuromelanized neurons in the substantia nigra pars compacta and α-synuclein-immunopositive inclusions (Lewy bodies) in several types of neurons in the brain. A fraction of monogenic PD cases, however, represent a conundrum, as they can present with clinical Lewy body disease but do not have Lewy bodies upon neuropathological examination. For LRRK2, the presence or absence of Lewy bodies is not related to any specific mutation in the gene and different clinical presentation and neuropathology can be present even in the same family. Here, we present the first evidence of widespread α-synuclein accumulation detected with proximity ligation assay (PLA) using the MJFR14-6-4-2 antibody in six Lewy body-negative LRRK2 cases and compare the levels with five patients with neuropathologically verified Lewy body disease and six healthy controls. We show that non-inclusion aggregated α-synuclein in the form of particulate PLA signal is dominant in the LRRK2 cases, while both Lewy-like and particulate PLA signal is found in late-stage Lewy body disease. Furthermore, LRRK2 cases displayed prominent particulate PLA signal in pontocerebellar tracts and inferior olivary nuclei in the brainstem, which was not seen in idiopathic Lewy body disease cases. These results suggest that Lewy-body negative LRRK2-related PD is not associated with a lack of α-synuclein aggregation in neurons but rather a deficiency in the formation of inclusions.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02871-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896665","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":"LRRK2-associated Parkinson’s disease does have alpha-synuclein pathology","authors":"Nicolas Dzamko","doi":"10.1007/s00401-025-02874-7","DOIUrl":"10.1007/s00401-025-02874-7","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896695","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":"Widespread distribution of α-synuclein oligomers in LRRK2-related Parkinson’s disease","authors":"Hiroaki Sekiya,&nbsp;Lukas Franke,&nbsp;Yuki Hashimoto,&nbsp;Mariko Takata,&nbsp;Katsuya Nishida,&nbsp;Naonobu Futamura,&nbsp;Kazuko Hasegawa,&nbsp;Hisatomo Kowa,&nbsp;Owen A. Ross,&nbsp;Pamela J. McLean,&nbsp;Tatsushi Toda,&nbsp;Zbigniew K. Wszolek,&nbsp;Dennis W. Dickson","doi":"10.1007/s00401-025-02872-9","DOIUrl":"10.1007/s00401-025-02872-9","url":null,"abstract":"<div><p>Mutations in leucine-rich repeat kinase 2 (<i>LRRK2</i>) are the most common cause of familial and sporadic Parkinson’s disease (PD). While the clinical features of patients with <i>LRRK2</i>-PD resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of patients with <i>LRRK2</i>-PD do not have Lewy-related pathology. Lewy-related pathology is a late-stage αSYN aggregation that can be visualized with hematoxylin and eosin stains or conventional immunohistochemistry (IHC). Increasing evidence has indicated that αSYN oligomers, which represent the early-stage of αSYN aggregation, may have neurotoxicity. Visualization of αSYN oligomers requires specialized staining techniques, such as αSYN-proximity ligation assay (PLA). Distribution and severity of αSYN oligomers in the brain of patients with <i>LRRK2</i>-PD remain unknown. In this study, we performed phosphorylated αSYN-IHC and αSYN-PLA staining on postmortem brain sections of patients with three pathogenic LRRK2 mutants: p.G2019S (<i>n</i> = 5), p.I2020T (<i>n</i> = 5), and p.R1441C (<i>n</i> = 4). The severity of Lewy-related pathology and αSYN oligomers was assessed semi-quantitatively in the brainstem, limbic lobe, basal ganglia, and cerebral cortex. αSYN oligomers were detected in patients with <i>LRRK2</i>-PD even in those without Lewy-related pathology; a negative correlation was observed between Lewy-related pathology and αSYN oligomers (<i>r</i> = − 0.26 [− 0.39, − 0.12]; <i>P</i> &lt; 0.0001). Our findings suggest that αSYN oligomers may represent a common pathological feature of <i>LRRK2</i>-PD. Notably, patients harboring p.G2019S and p.I2020T had significantly higher levels of αSYN oligomers in those without Lewy-related pathology compared to those with Lewy-related pathology. These patients also had a trend toward shorter disease duration. These results imply that in <i>LRRK2</i>-PD, αSYN oligomers may initially accumulate in the brain but do not progress to form Lewy-related pathology. The present study suggests that targeting αSYN oligomers may be a therapeutic strategy for <i>LRRK2</i>-PD even if there is no Lewy-related pathology.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896660","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":"CAA proteomics meta-analysis reveals novel targets, key players, and the effects of sex, APOE, and brain region in humans","authors":"Curran Varma,&nbsp;Cynthia A. Lemere","doi":"10.1007/s00401-025-02886-3","DOIUrl":"10.1007/s00401-025-02886-3","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02886-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884695","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":"Spatial mapping of the AA-PGE2-EP axis in multiple sclerosis lesions","authors":"Cathrin E. Hansen,&nbsp;Julia Konings,&nbsp;Gabor Toth,&nbsp;Serhii Chornyi,&nbsp;Manon Karsten,&nbsp;Bert van het Hof,&nbsp;Susanne M. A. van der Pol,&nbsp;Stephanie D. Beekhuis-Hoekstra,&nbsp;Nine Kok,&nbsp;Wing Ka Fung,&nbsp;Naomi S. Dijksman,&nbsp;Wia Baron,&nbsp;Maarten E. Witte,&nbsp;Ingela Lanekoff,&nbsp;Helga E. de Vries,&nbsp;Gijs Kooij","doi":"10.1007/s00401-025-02878-3","DOIUrl":"10.1007/s00401-025-02878-3","url":null,"abstract":"<div><p>Bioactive lipid mediators (LMs) derived from polyunsaturated fatty acids (PUFAs) are key molecules in both the initiation and resolution of inflammatory responses. Previous findings suggest that a dysregulated LM balance, especially within the arachidonic acid (AA) pathway, may contribute to an impaired resolution response and subsequent chronic neuroinflammation in multiple sclerosis (MS). However, to date, the local biosynthesis and signaling of LMs within the brain of people with MS (PwMS) remains unexplored. In this study, we, therefore, mapped the distribution of AA and its key downstream LM prostaglandin E₂ (PGE₂) in white matter MS brain tissue and of non-neurological controls (NNCs) for the first time using mass spectrometry imaging. We found that AA levels are lower in MS cases compared to NNCs and reduced in MS lesions compared to peri-lesional tissue. Furthermore, the PGE₂/AA ratio, indicating the PGE₂ synthesis from the AA substrate, was increased in lesion areas compared to fully myelinated regions in MS. In line with that, the expression of prostaglandin synthesizing enzymes as measured by RT-qPCR was partially increased in MS tissue compared to NNCs. In addition, the expression of prostaglandin E2 receptor 4 (EP4) decreased, while prostaglandin E2 receptor 2 (EP2) showed increased expression levels in MS lesions compared to NNCs and localized specifically to microglia. We also found that PGE₂ addition to pro-inflammatory human-induced pluripotent stem cell (iPSC)-derived microglia resulted in enhanced cytokine signaling pathways, but also the upregulation of its synthase <i>PTGES</i> and homeostatic/resolving signaling, the latter of which might mainly occur through EP2 signaling. Collectively, our results provide detailed information about the region-specific levels of AA and PGE₂ in MS lesions and we propose enhanced PGE₂-EP2 signaling in inflamed microglia in MS.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02878-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883708","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":"LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP","authors":"Ryan K. Shahidehpour,&nbsp;Yuriko Katsumata,&nbsp;Dennis W. Dickson,&nbsp;Nikhil B. Ghayal,&nbsp;Khine Zin Aung,&nbsp;Xian Wu,&nbsp;Panhavuth Phe,&nbsp;Gregory A. Jicha,&nbsp;Allison M. Neltner,&nbsp;Jessalin R. C. Archer,&nbsp;Maria M. Corrada,&nbsp;Claudia H. Kawas,&nbsp;S. Ahmad Sajjadi,&nbsp;Davis C. Woodworth,&nbsp;Syed A. Bukhari,&nbsp;Thomas J. Montine,&nbsp;David W. Fardo,&nbsp;Peter T. Nelson","doi":"10.1007/s00401-025-02876-5","DOIUrl":"10.1007/s00401-025-02876-5","url":null,"abstract":"<div><p>A diagnostic rubric is required to distinguish between limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In LATE-NC Stage 3, TDP-43 proteinopathy is present in the middle frontal gyrus (MFG), thus posing a potential diagnostic challenge in differentiating these severe LATE-NC cases from FTLD-TDP. LATE-NC Stage 3 cases and other TDP-43 proteinopathies were analyzed from the University of Kentucky (total n = 514 with TDP-43 pathology assessed), The 90+ Study at the University of California Irvine (n = 458), and the Mayo Clinic (n = 5067) brain banks. Digital pathology was used to quantify pathology burden in a select subset of cases (n = 51), complemented by a previously-described manual counting method and expert neuropathologic examinations to evaluate qualitative features such as FTLD-TDP types and subtypes of neuronal cytoplasmic inclusions (NCIs). To evaluate clinical and genetic characteristics of LATE-NC Stage 3, data were analyzed from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data set and correlated with findings from the Alzheimer’s Disease Genetics Consortium (ADGC). When using TDP-43 proteinopathy quantification in the MFG as a diagnostic criterion, more than 90% of cases could be classified as either LATE-NC Stage 3 or FTLD-TDP. Diagnostically challenging scenarios included a subset of FTLD-TDP Type B cases with relatively mild MFG TDP-43 pathology and a novel non-LATE-NC, non-FTLD-TDP pathologic subtype with severe MFG TDP-43 pathology. Taking these potential pitfalls into account, a classification schema was developed that could correctly diagnose all included cases. There was no difference in the Alzheimer’s disease pathological load in LATE-NC Stages 2 versus 3. In genetic analyses, the <i>GRN</i> (rs5848) risk allele was preferentially associated with LATE-NC Stage 3, whereas <i>TMEM106B</i> and <i>APOE</i> risk-associated variants were not. In conclusion, LATE-NC Stage 3 could be differentiated reliably from FTLD-TDP and other TDP-43-opathies, based on a data-driven diagnostic rubric.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02876-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879748","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":"Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change","authors":"Osamu Yokota,&nbsp;Tomoko Miki,&nbsp;Hanae Nakashima-Yasuda,&nbsp;Hideki Ishizu,&nbsp;Takashi Haraguchi,&nbsp;Akinori Miyashita,&nbsp;Takeshi Ikeuchi,&nbsp;Masato Hasegawa,&nbsp;Naoto Nishikawa,&nbsp;Shintaro Takenoshita,&nbsp;Seishi Terada,&nbsp;Manabu Takaki","doi":"10.1007/s00401-025-02875-6","DOIUrl":"10.1007/s00401-025-02875-6","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02875-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875318","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}