Acta Neuropathologica最新文献

{"title":"Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas","authors":"Justin Z. Wang,&nbsp;Vikas Patil,&nbsp;Jeff Liu,&nbsp;Helin Dogan,&nbsp;Ghazaleh Tabatabai,&nbsp;Leeor S. Yefet,&nbsp;Felix Behling,&nbsp;Elgin Hoffman,&nbsp;Severa Bunda,&nbsp;Rebecca Yakubov,&nbsp;Ramneet Kaloti,&nbsp;Sebastian Brandner,&nbsp;Andrew Gao,&nbsp;Aaron Cohen-Gadol,&nbsp;Jill Barnholtz-Sloan,&nbsp;Marco Skardelly,&nbsp;Marcos Tatagiba,&nbsp;David R. Raleigh,&nbsp;Felix Sahm,&nbsp;Paul C. Boutros,&nbsp;Kenneth Aldape,&nbsp;The International Consortium on Meningiomas (ICOM),&nbsp;Farshad Nassiri,&nbsp;Gelareh Zadeh","doi":"10.1007/s00401-023-02571-3","DOIUrl":"10.1007/s00401-023-02571-3","url":null,"abstract":"<div><p>Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2A^high) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2A^high meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"146 1","pages":"145 - 162"},"PeriodicalIF":12.7,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02571-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670410","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":"Transcriptome analysis stratifies second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes","authors":"Andrey Korshunov,&nbsp;Konstantin Okonechnikov,&nbsp;Daniel Schrimpf,&nbsp;Svenja Tonn,&nbsp;Martin Mynarek,&nbsp;Jan Koster,&nbsp;Philipp Sievers,&nbsp;Till Milde,&nbsp;Felix Sahm,&nbsp;David T. W. Jones,&nbsp;Andreas von Deimling,&nbsp;Stefan M. Pfister,&nbsp;Marcel Kool","doi":"10.1007/s00401-023-02575-z","DOIUrl":"10.1007/s00401-023-02575-z","url":null,"abstract":"<div><p>Medulloblastoma (MB), one of the most common malignant pediatric brain tumor, is a heterogenous disease comprised of four distinct molecular groups (WNT, SHH, Group 3, Group 4). Each of these groups can be further subdivided into second-generation MB (SGS MB) molecular subgroups, each with distinct genetic and clinical characteristics. For instance, non-WNT/non-SHH MB (Group 3/4) can be subdivided molecularly into eight distinct and clinically relevant tumor subgroups. A further molecular stratification/summarization of these SGS MB would allow for the assignment of patients to risk-associated treatment protocols. Here, we performed DNA- and RNA-based analysis of 574 non-WNT/non-SHH MB and analyzed the clinical significance of various molecular patterns within the entire cohort and the eight SGS MB, with the aim to develop an optimal risk stratification of these tumors. Multigene analysis disclosed several survival-associated genes highly specific for each molecular subgroup within this non-WNT/non-SHH MB cohort with minimal inter-subgroup overlap. These subgroup-specific and prognostically relevant genes were associated with pathways that could underlie SGS MB clinical-molecular diversity and tumor-driving mechanisms. By combining survival-associated genes within each SGS MB, distinct metagene sets being appropriate for their optimal risk stratification were identified. Defined subgroup-specific metagene sets were independent variables in the multivariate models generated for each SGS MB and their prognostic value was confirmed in a completely non-overlapping validation cohort of non-WNT/non-SHH MB (<i>n</i> = 377). In summary, the current results indicate that the integration of transcriptome data in risk stratification models may improve outcome prediction for each non-WNT/non-SHH SGS MB. Identified subgroup-specific gene expression signatures could be relevant for clinical implementation and survival-associated metagene sets could be adopted for further SGS MB risk stratification. Future studies should aim at validating the prognostic role of these transcriptome-based SGS MB subtypes in prospective clinical trials.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"829 - 842"},"PeriodicalIF":12.7,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02575-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9501692","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 perils of contact sport: pathologies of diffuse brain swelling and chronic traumatic encephalopathy neuropathologic change in a 23-year-old rugby union player","authors":"Edward B. Lee,&nbsp;Claire Kennedy-Dietrich,&nbsp;Jennian F. Geddes,&nbsp;James A. R. Nicoll,&nbsp;Tamas Revesz,&nbsp;Douglas H. Smith,&nbsp;William Stewart","doi":"10.1007/s00401-023-02576-y","DOIUrl":"10.1007/s00401-023-02576-y","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"847 - 850"},"PeriodicalIF":12.7,"publicationDate":"2023-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02576-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561507","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 to: Dysregulation of astrocytic Ca2+ signaling and gliotransmitter release in mouse models of α-synucleinopathies","authors":"Carmen Nanclares,&nbsp;Jonah Poynter,&nbsp;Hector A. Martell-Martinez,&nbsp;Scott Vermilyea,&nbsp;Alfonso Araque,&nbsp;Paulo Kofuji,&nbsp;Michael K. Lee,&nbsp;Ana Covelo","doi":"10.1007/s00401-023-02573-1","DOIUrl":"10.1007/s00401-023-02573-1","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"857 - 857"},"PeriodicalIF":12.7,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02573-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50500553","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":"Loss of hypothalamic MCH decreases food intake in amyotrophic lateral sclerosis","authors":"Matei Bolborea,&nbsp;Pauline Vercruysse,&nbsp;Tselmen Daria,&nbsp;Johanna C. Reiners,&nbsp;Najwa Ouali Alami,&nbsp;Simon J. Guillot,&nbsp;Stéphane Dieterlé,&nbsp;Jérôme Sinniger,&nbsp;Jelena Scekic-Zahirovic,&nbsp;Amela Londo,&nbsp;Hippolyte Arcay,&nbsp;Marc-Antoine Goy,&nbsp;Claudia Nelson de Tapia,&nbsp;Dietmar R. Thal,&nbsp;Kazumoto Shibuya,&nbsp;Ryo Otani,&nbsp;Kimihito Arai,&nbsp;Satoshi Kuwabara,&nbsp;Albert C. Ludolph,&nbsp;Francesco Roselli,&nbsp;Deniz Yilmazer-Hanke,&nbsp;Luc Dupuis","doi":"10.1007/s00401-023-02569-x","DOIUrl":"10.1007/s00401-023-02569-x","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) is associated with impaired energy metabolism, including weight loss and decreased appetite which are negatively correlated with survival. Neural mechanisms underlying metabolic impairment in ALS remain unknown. ALS patients and presymptomatic gene carriers have early hypothalamic atrophy. The lateral hypothalamic area (LHA) controls metabolic homeostasis through the secretion of neuropeptides such as orexin/hypocretin and melanin-concentrating hormone (MCH). Here, we show loss of MCH-positive neurons in three mouse models of ALS based on <i>SOD1</i> or <i>FUS</i> mutations. Supplementation with MCH (1.2 µg/d) through continuous intracerebroventricular delivery led to weight gain in male mutant <i>Sod1</i>^<i>G86R</i> mice. MCH supplementation increased food intake, rescued expression of the key appetite-related neuropeptide AgRP (agouti-related protein) and modified respiratory exchange ratio, suggesting increased carbohydrate usage during the inactive phase. Importantly, we document pTDP-43 pathology and neurodegeneration in the LHA of sporadic ALS patients. Neuronal cell loss was associated with pTDP-43-positive inclusions and signs of neurodegeneration in MCH-positive neurons. These results suggest that hypothalamic MCH is lost in ALS and contributes to the metabolic changes, including weight loss and decreased appetite.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"773 - 791"},"PeriodicalIF":12.7,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02569-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9617739","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":"Plasma p-tau181 and p-tau217 in discriminating PART, AD and other key neuropathologies in older adults","authors":"Lei Yu,&nbsp;Patricia A. Boyle,&nbsp;Shorena Janelidze,&nbsp;Vladislav A. Petyuk,&nbsp;Tianhao Wang,&nbsp;David A. Bennett,&nbsp;Oskar Hansson,&nbsp;Julie A. Schneider","doi":"10.1007/s00401-023-02570-4","DOIUrl":"10.1007/s00401-023-02570-4","url":null,"abstract":"<div><p>We examined whether plasma p-tau181 and p-tau217 are specific biomarkers of pathologically confirmed Alzheimer’s disease (AD). In particular, we investigated the utility of plasma p-tau for differentiating AD from primary age-related tauopathy (PART), as well as AD with mixed pathologies. Data came from 269 older adults who participated in the Religious Orders Study or the Rush Memory and Aging Project. Blood samples were collected during annual clinical evaluations. Participants died and underwent brain autopsy. P-tau181 and p-tau217 were quantified in the plasma samples proximate to death (average interval before death: 1.4 years) using Lilly-developed MSD immunoassays. Uniform neuropathologic evaluations assessed AD, PART, and other common degenerative and cerebrovascular conditions. Plasma p-tau217 was more strongly correlated with brain β-amyloid and paired helical filament tau (PHFtau) tangles than p-tau181. Both p-tau markers were associated with greater odds of AD, but p-tau217 had higher accuracy (area under the ROC curve (AUC): 0.83) than p-tau181 (AUC: 0.76). Plasma p-tau markers were almost exclusively associated with AD pathologic indices with the exception of cerebral amyloid angiopathy. Compared to p-tau181, p-tau217 showed a higher AUC (0.82 versus 0.74) in differentiating AD from PART. For either p-tau, we did not observe a level difference between individuals with AD alone and those with mixed AD pathologies. In summary, plasma p-tau181and p-tau217 were specifically associated with AD pathological changes. Further, our data provide initial evidence that p-tau217 may be able to differentiate between AD and PART in individuals with comparable burdens of tau tangle pathology. These results demonstrate the specificity of p-tau217 for AD, supporting its use to identify patients suitable for anti-AD therapies including β-amyloid immunotherapies.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"146 1","pages":"1 - 11"},"PeriodicalIF":12.7,"publicationDate":"2023-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02570-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636749","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":"Molecular integrators of stress and aging: the example of FKBP5","authors":"Anthony S. Zannas","doi":"10.1007/s00401-023-02572-2","DOIUrl":"10.1007/s00401-023-02572-2","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"713 - 715"},"PeriodicalIF":12.7,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536229","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":"Clinical applicability of miR517a detection in liquid biopsies of ETMR patients","authors":"Sibylle Madlener,&nbsp;Julia Furtner,&nbsp;Natalia Stepien,&nbsp;Daniel Senfter,&nbsp;Lisa Mayr,&nbsp;Maximilian Zeyda,&nbsp;Leon Gramss,&nbsp;Barbara Aistleitner,&nbsp;Sabine Spiegl-Kreinecker,&nbsp;Elisa Rivelles,&nbsp;Christian Dorfer,&nbsp;Karl Rössler,&nbsp;Thomas Czech,&nbsp;Amedeo A. Azizi,&nbsp;Andreas Peyrl,&nbsp;Daniela Lötsch-Gojo,&nbsp;Leonhard Müllauer,&nbsp;Christine Haberler,&nbsp;Irene Slavc,&nbsp;Johannes Gojo","doi":"10.1007/s00401-023-02567-z","DOIUrl":"10.1007/s00401-023-02567-z","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 6","pages":"843 - 846"},"PeriodicalIF":12.7,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02567-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542516","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":"Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification","authors":"Jack Goddard,&nbsp;Jemma Castle,&nbsp;Emily Southworth,&nbsp;Anya Fletcher,&nbsp;Stephen Crosier,&nbsp;Idoia Martin-Guerrero,&nbsp;Miguel García-Ariza,&nbsp;Aurora Navajas,&nbsp;Julien Masliah-Planchon,&nbsp;Franck Bourdeaut,&nbsp;Christelle Dufour,&nbsp;Olivier Ayrault,&nbsp;Tobias Goschzik,&nbsp;Torsten Pietsch,&nbsp;Martin Sill,&nbsp;Stefan M. Pfister,&nbsp;Stefan Rutkowski,&nbsp;Stacey Richardson,&nbsp;Rebecca M. Hill,&nbsp;Daniel Williamson,&nbsp;Simon Bailey,&nbsp;Edward C. Schwalbe,&nbsp;Steven C. Clifford,&nbsp;Debbie Hicks","doi":"10.1007/s00401-023-02566-0","DOIUrl":"10.1007/s00401-023-02566-0","url":null,"abstract":"<div><p>Group 4 tumours (MB_Grp4) represent the majority of non-WNT/non-SHH medulloblastomas. Their clinical course is poorly predicted by current risk-factors. MB_Grp4 molecular substructures have been identified (e.g. subgroups/cytogenetics/mutations), however their inter-relationships and potential to improve clinical sub-classification and risk-stratification remain undefined. We comprehensively characterised the paediatric MB_Grp4 molecular landscape and determined its utility to improve clinical management. A clinically-annotated discovery cohort (n = 362 MB_Grp4) was assembled from UK-CCLG institutions and SIOP-UKCCSG-PNET3, HIT-SIOP-PNET4 and PNET HR + 5 clinical trials. Molecular profiling was undertaken, integrating driver mutations, second-generation non-WNT/non-SHH subgroups (1–8) and whole-chromosome aberrations (WCAs). Survival models were derived for patients ≥ 3 years of age who received contemporary multi-modal therapies (n = 323). We first independently derived and validated a favourable-risk WCA group (WCA-FR) characterised by ≥ 2 features from chromosome 7 gain, 8 loss, and 11 loss. Remaining patients were high-risk (WCA-HR). Subgroups 6 and 7 were enriched for WCA-FR (p &lt; 0·0001) and aneuploidy. Subgroup 8 was defined by predominantly balanced genomes with isolated isochromosome 17q (p &lt; 0·0001). While no mutations were associated with outcome and overall mutational burden was low, WCA-HR harboured recurrent chromatin remodelling mutations (p = 0·007). Integration of methylation and WCA groups improved risk-stratification models and outperformed established prognostication schemes. Our MB_Grp4 risk-stratification scheme defines: favourable-risk (non-metastatic disease and (i) subgroup 7 or (ii) WCA-FR (21% of patients, 5-year PFS 97%)), very-high-risk (metastatic disease with WCA-HR (36%, 5-year PFS 49%)) and high-risk (remaining patients; 43%, 5-year PFS 67%). These findings validated in an independent MB_Grp4 cohort (n = 668). Importantly, our findings demonstrate that previously established disease-wide risk-features (i.e. LCA histology and <i>MYC(N)</i> amplification) have little prognostic relevance in MB_Grp4 disease. Novel validated survival models, integrating clinical features, methylation and WCA groups, improve outcome prediction and re-define risk-status for ~ 80% of MB_Grp4. Our MB_Grp4 favourable-risk group has MB_WNT-like excellent outcomes, thereby doubling the proportion of medulloblastoma patients who could benefit from therapy de-escalation approaches, aimed at reducing treatment induced late-effects while sustaining survival outcomes. Novel approaches are urgently required for the very-high-risk patients.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 5","pages":"651 - 666"},"PeriodicalIF":12.7,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02566-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336943","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":"Biomarkers for parkinsonian disorders in CNS-originating EVs: promise and challenges","authors":"Suman Dutta,&nbsp;Simon Hornung,&nbsp;Hash Brown Taha,&nbsp;Gal Bitan","doi":"10.1007/s00401-023-02557-1","DOIUrl":"10.1007/s00401-023-02557-1","url":null,"abstract":"<div><p>Extracellular vesicles (EVs), including exosomes, microvesicles, and oncosomes, are nano-sized particles enclosed by a lipid bilayer. EVs are released by virtually all eukaryotic cells and have been shown to contribute to intercellular communication by transporting proteins, lipids, and nucleic acids. In the context of neurodegenerative diseases, EVs may carry toxic, misfolded forms of amyloidogenic proteins and facilitate their spread to recipient cells in the central nervous system (CNS). CNS-originating EVs can cross the blood–brain barrier into the bloodstream and may be found in other body fluids, including saliva, tears, and urine. EVs originating in the CNS represent an attractive source of biomarkers for neurodegenerative diseases, because they contain cell- and cell state-specific biological materials. In recent years, multiple papers have reported the use of this strategy for identification and quantitation of biomarkers for neurodegenerative diseases, including Parkinson’s disease and atypical parkinsonian disorders. However, certain technical issues have yet to be standardized, such as the best surface markers for isolation of cell type-specific EVs and validating the cellular origin of the EVs. Here, we review recent research using CNS-originating EVs for biomarker studies, primarily in parkinsonian disorders, highlight technical challenges, and propose strategies for overcoming them.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"145 5","pages":"515 - 540"},"PeriodicalIF":12.7,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-023-02557-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698765","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}