Brain Pathology最新文献

{"title":"Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells","authors":"Veronica Astillero-Lopez,&nbsp;Sandra Villar-Conde,&nbsp;Melania Gonzalez-Rodriguez,&nbsp;Alicia Flores-Cuadrado,&nbsp;Isabel Ubeda-Banon,&nbsp;Daniel Saiz-Sanchez,&nbsp;Alino Martinez-Marcos","doi":"10.1111/bpa.13235","DOIUrl":"10.1111/bpa.13235","url":null,"abstract":"<p>Alzheimer's disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-β (Aβ) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron–glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and non-AD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aβ and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aβ and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aβ plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells in the human EC in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511862","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":"Induced pluripotent stem cell models as a tool to investigate and test fluid biomarkers in Alzheimer's disease and frontotemporal dementia","authors":"Julie J. McInvale,&nbsp;Peter Canoll,&nbsp;Gunnar Hargus","doi":"10.1111/bpa.13231","DOIUrl":"10.1111/bpa.13231","url":null,"abstract":"<p>Neurodegenerative diseases are increasing in prevalence and comprise a large socioeconomic burden on patients and their caretakers. The need for effective therapies and avenues for disease prevention and monitoring is of paramount importance. Fluid biomarkers for neurodegenerative diseases have gained a variety of uses, including informing participant selection for clinical trials, lending confidence to clinical diagnosis and disease staging, determining prognosis, and monitoring therapeutic response. Their role is expected to grow as disease-modifying therapies start to be available to a broader range of patients and as prevention strategies become established. Many of the underlying molecular mechanisms of currently used biomarkers are incompletely understood. Animal models and in vitro systems using cell lines have been extensively employed but face important translatability limitations. Induced pluripotent stem cell (iPSC) technology, where a theoretically unlimited range of cell types can be reprogrammed from peripheral cells sampled from patients or healthy individuals, has gained prominence over the last decade. It is a promising avenue to study physiological and pathological biomarker function and response to experimental therapeutics. Such systems are amenable to high-throughput drug screening or multiomics readouts such as transcriptomics, lipidomics, and proteomics for biomarker discovery, investigation, and validation. The present review describes the current state of biomarkers in the clinical context of neurodegenerative diseases, with a focus on Alzheimer's disease and frontotemporal dementia. We include a discussion of how iPSC models have been used to investigate and test biomarkers such as amyloid-β, phosphorylated tau, neurofilament light chain or complement proteins, and even nominate novel biomarkers. We discuss the limitations of current iPSC methods, mentioning alternatives such as coculture systems and three-dimensional organoids which address some of these concerns. Finally, we propose exciting prospects for stem cell transplantation paradigms using animal models as a preclinical tool to study biomarkers in the in vivo context.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511860","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":"Phenotype parallels protein seeding capacity in neurodegenerative diseases","authors":"Ivan Martinez-Valbuena","doi":"10.1111/bpa.13238","DOIUrl":"10.1111/bpa.13238","url":null,"abstract":"<p>With the new era of disease-modifying therapies for neurodegenerative diseases, a novel approach for the molecular classification of neurodegenerative diseases is needed. In this research letter, there is a summary of the advances made in Alzheimer's disease, Lewy body disorders, and progressive supranuclear palsy toward this classification.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139429262","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":"Diagnostic utility of genetic alterations in distinguishing IDH-wildtype glioblastoma from lower-grade gliomas: Insight from next-generation sequencing analysis of 479 cases","authors":"Boram Lee,&nbsp;Soohyun Hwang,&nbsp;Hyunsik Bae,&nbsp;Kyue-Hee Choi,&nbsp;Yeon-Lim Suh","doi":"10.1111/bpa.13234","DOIUrl":"10.1111/bpa.13234","url":null,"abstract":"<p>The accurate diagnosis and classification of gliomas are essential for appropriate treatment planning and prognosis prediction. This study aimed to investigate the molecular diagnostics of IDH-wildtype diffuse astrocytic gliomas and identify potential genetic variants that could differentiate glioblastoma (GBM) from lower-grade gliomas when DNA methylation analysis is not feasible. In total, 479 H3-and IDH-wildtype diffuse astrocytic gliomas were included in this study. All the cases were diagnosed according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Panel sequencing data were collected, and clinicopathological information was retrieved from medical records. Genetic alterations and histological findings were analyzed to determine their diagnostic utility and prognostic implications. Out of 479 cases, 439 (91.6%) were diagnosed with GBM, including 28 cases that were molecularly diagnosed as GBM. However, 40 (8.4%) cases could not be classified according to the 2021 WHO classification and were diagnosed as lower-grade diffuse astrocytic glioma, IDH-wildtype, not elsewhere classified (LGNEC). In addition to the three genetic alterations included in the diagnostic criteria of GBM, <i>PTEN</i> and <i>EGFR</i> mutations were found to be enriched in GBM. Patients harboring mTOR pathway mutations demonstrated a more favorable prognosis and often exhibited morphology resembling subependymal giant cell astrocytoma, along with a high tumor mutational burden. Among patients with mTOR pathway mutations, those lacking molecular diagnostic features of GBM exhibited outstanding survival outcomes, even in the presence of grade 4 histology. Integration of molecular features enhanced the diagnostic accuracy of IDH-wildtype gliomas. Some molecular alterations enriched in GBM offer valuable insights for molecular diagnosis and glioma classification. Furthermore, high-grade diffuse astrocytic gliomas featuring mTOR pathway mutations in the absence of molecular diagnostic features of GBM could represent more favorable tumor types distinct from GBM.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139461725","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":"Morphology-based molecular classification of spinal cord ependymomas using deep neural networks","authors":"Yannis Schumann,&nbsp;Matthias Dottermusch,&nbsp;Leonille Schweizer,&nbsp;Maja Krech,&nbsp;Tasja Lempertz,&nbsp;Ulrich Schüller,&nbsp;Philipp Neumann,&nbsp;Julia E. Neumann","doi":"10.1111/bpa.13239","DOIUrl":"10.1111/bpa.13239","url":null,"abstract":"<p>Based on DNA-methylation, ependymomas growing in the spinal cord comprise two major molecular types termed spinal (SP-EPN) and myxopapillary ependymomas (MPE(-A/B)), which differ with respect to their clinical features and prognosis. Due to the existing discrepancy between histomorphogical diagnoses and classification using methylation data, we asked whether deep neural networks can predict the DNA methylation class of spinal cord ependymomas from hematoxylin and eosin stained whole-slide images. Using explainable AI, we further aimed to prospectively improve the consistency of histology-based diagnoses with DNA methylation profiling by identifying and quantifying distinct morphological patterns of these molecular ependymoma types. We assembled a case series of 139 molecularly characterized spinal cord ependymomas (<i>n</i>_MPE = 84, <i>n</i>_SP-EPN = 55). Self-supervised and weakly-supervised neural networks were used for classification. We employed attention analysis and supervised machine-learning methods for the discovery and quantification of morphological features and their correlation to the diagnoses of experienced neuropathologists. Our best performing model predicted the DNA methylation class with 98% test accuracy and used self-supervised learning to outperform pretrained encoder-networks (86% test accuracy). In contrast, the diagnoses of neuropathologists matched the DNA methylation class in only 83% of cases. Domain-adaptation techniques improved model generalization to an external validation cohort by up to 22%. Statistically significant morphological features were identified per molecular type and quantitatively correlated to human diagnoses. The approach was extended to recently defined subtypes of myxopapillary ependymomas (MPE-(A/B), 80% test accuracy). In summary, we demonstrated the accurate prediction of the DNA methylation class of spinal cord ependymomas (SP-EPN, MPE(-A/B)) using hematoxylin and eosin stained whole-slide images. Our approach may prospectively serve as a supplementary resource for integrated diagnostics and may even help to establish a standardized, high-quality level of histology-based diagnostics across institutions—in particular in low-income countries, where expensive DNA-methylation analyses may not be readily available.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416413","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":"Understanding the pathogenic mechanisms and therapeutic effects in neurocysticercosis","authors":"Gino Castillo,&nbsp;Lizbeth Fustamante,&nbsp;Ana D. Delgado-Kamiche,&nbsp;Rogger P. Camen-Orozco,&nbsp;Taryn Clark,&nbsp;Edson Bernal,&nbsp;Jemima Morales-Alvarez,&nbsp;Maria Ferrufino,&nbsp;Javier Mamani-Palomino,&nbsp;Javier A. Bustos,&nbsp;Hector H. Garcia,&nbsp;Cesar M. Gavidia,&nbsp;Robert H. Gilman,&nbsp;Manuela Verastegui,&nbsp;Cysticercosis Working Group in Peru","doi":"10.1111/bpa.13237","DOIUrl":"10.1111/bpa.13237","url":null,"abstract":"<p>Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with <i>Taenia solium</i> oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, <i>p</i> &lt; 0.0001), higher spheroids count (45.2 vs. 0.2, <i>p</i> = 0.0001), and increased inflammation (72.0% vs. 21.4%, <i>p</i> = 0.003). In this rat model, <i>anthelmintic treatment destroyed</i> brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139429263","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":"The post-stroke young adult brain has limited capacity to re-express the gene expression patterns seen during early postnatal brain development","authors":"Mihai Ruscu,&nbsp;Bogdan Capitanescu,&nbsp;Paul Rupek,&nbsp;Thomas Dandekar,&nbsp;Eugen Radu,&nbsp;Dirk M. Hermann,&nbsp;Aurel Popa-Wagner","doi":"10.1111/bpa.13232","DOIUrl":"10.1111/bpa.13232","url":null,"abstract":"<p>The developmental origins of the brain's response to injury can play an important role in recovery after a brain lesion. In this study, we investigated whether the ischemic young adult brain can re-express brain plasticity genes that were active during early postnatal development. Differentially expressed genes in the cortex of juvenile post-natal day 3 and the peri-infarcted cortical areas of young, 3-month-old post-stroke rats were identified using fixed-effects modeling within an empirical Bayes framework through condition-specific comparison. To further analyze potential biological processes, upregulated and downregulated genes were assessed for enrichment using GSEA software. The genes showing the highest expression changes were subsequently verified through RT-PCR. Our findings indicate that the adult brain partially recapitulates the gene expression profile observed in the juvenile brain but fails to upregulate many genes and pathways necessary for brain plasticity. Of the upregulated genes in post-stroke brains, specific roles have not been assigned to <i>Apobec1, Cenpf</i>, <i>Ect2</i>, <i>Folr2</i>, <i>Glipr1</i>, <i>Myo1f</i>, <i>and Pttg1</i>. New genes that failed to upregulate in the adult post-stroke brain include <i>Bex4</i>, <i>Cd24</i>, <i>Klhl1</i>/<i>Mrp2</i>, <i>Trim67</i>, <i>and St8sia2</i>. Among the upregulated pathways, the largest change was observed in the KEGG pathway “One carbon pool of folate,” which is necessary for cellular proliferation, followed by the KEGG pathway “Antifolate resistance,” whose genes mainly encode the family of ABC transporters responsible for the efflux of drugs that have entered the brain. We also noted three less-described downregulated KEGG pathways in experimental models: glycolipid biosynthesis, oxytocin, and cortisol pathways, which could be relevant as therapeutic targets. The limited brain plasticity of the adult brain is illustrated through molecular and histological analysis of the axonal growth factor, KIF4. Collectively, these results strongly suggest that further research is needed to decipher the complex genetic mechanisms that prevent the re-expression of brain plasticity-associated genes in the adult brain.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416414","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":"Refinement of prognostication for IDH-mutant astrocytomas using DNA methylation-based classification","authors":"Teresia Kling,&nbsp;Sandra Ferreyra Vega,&nbsp;Medha Suman,&nbsp;Anna Dénes,&nbsp;Anna Lipatnikova,&nbsp;Stina Lagerström,&nbsp;Thomas Olsson Bontell,&nbsp;Asgeir Store Jakola,&nbsp;Helena Carén","doi":"10.1111/bpa.13233","DOIUrl":"10.1111/bpa.13233","url":null,"abstract":"<p>The 2021 World Health Organization (WHO) grading system of isocitrate dehydrogenase (<i>IDH</i>)-mutant astrocytomas relies on histological features and the presence of homozygous deletion of the cyclin-dependent kinase inhibitor 2A and 2B (<i>CDKN2A/B</i>). DNA methylation profiling has become highly relevant in the diagnosis of central nervous system (CNS) tumors including gliomas, and it has been incorporated into routine clinical diagnostics in some countries. In this study, we, therefore, examined the value of DNA methylation-based classification for prognostication of patients with <i>IDH</i>-mutant astrocytomas. We analyzed histopathological diagnoses, genome-wide DNA methylation array data, and chromosomal copy number alteration profiles from a cohort of 385 adult-type <i>IDH</i>-mutant astrocytomas, including a local cohort of 127 cases and 258 cases from public repositories. Prognosis based on WHO 2021 CNS criteria (histological grade and <i>CDKN2A/B</i> homozygous deletion status), other relevant chromosomal/gene alterations in <i>IDH</i>-mutant astrocytomas and DNA methylation-based subclassification according to the molecular neuropathology classifier were assessed. We demonstrate that DNA methylation-based classification of <i>IDH</i>-mutant astrocytomas can be used to predict outcome of the patients equally well as WHO 2021 CNS criteria. In addition, methylation-based subclassification enabled the identification of <i>IDH</i>-mutant astrocytoma patients with poor survival among patients with grade 3 tumors and patients with grade 4 tumors with a more favorable outcome. In conclusion, DNA methylation-based subclassification adds prognostic information for <i>IDH</i>-mutant astrocytomas that can further refine the current WHO 2021 grading scheme for these patients.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085954","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":"Distribution of ubiquilin 2 and TDP-43 aggregates throughout the CNS in UBQLN2 p.T487I-linked amyotrophic lateral sclerosis and frontotemporal dementia","authors":"Laura R. Nementzik,&nbsp;Kyrah M. Thumbadoo,&nbsp;Helen C. Murray,&nbsp;David Gordon,&nbsp;Shu Yang,&nbsp;Ian P. Blair,&nbsp;Clinton Turner,&nbsp;Richard L. M. Faull,&nbsp;Maurice A. Curtis,&nbsp;Catriona McLean,&nbsp;Garth A. Nicholson,&nbsp;Molly E. V. Swanson,&nbsp;Emma L. Scotter","doi":"10.1111/bpa.13230","DOIUrl":"10.1111/bpa.13230","url":null,"abstract":"<p>Mutations in the <i>UBQLN2</i> gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The neuropathology of such <i>UBQLN2</i>-linked cases of ALS/FTD is characterised by aggregates of the ubiquilin 2 protein in addition to aggregates of the transactive response DNA-binding protein of 43 kDa (TDP-43). ALS and FTD without <i>UBQLN2</i> mutations are also characterised by TDP-43 aggregates, that may or may not colocalise with wildtype ubiquilin 2. Despite this, the relative contributions of TDP-43 and ubiquilin 2 to disease pathogenesis remain largely under-characterised, as does their relative deposition as aggregates across the central nervous system (CNS). Here we conducted multiplex immunohistochemistry of three <i>UBQLN2</i> p.T487I-linked ALS/FTD cases, three non-<i>UBQLN2</i>-linked (sporadic) ALS cases, and 8 non-neurodegenerative disease controls, covering 40 CNS regions. We then quantified ubiquilin 2 aggregates, TDP-43 aggregates and aggregates containing both proteins in regions of interest to determine how <i>UBQLN2</i>-linked and non-<i>UBQLN2</i>-linked proteinopathy differ. We find that ubiquilin 2 aggregates that are negative for TDP-43 are predominantly small and punctate and are abundant in the hippocampal formation, spinal cord, all tested regions of neocortex, medulla and substantia nigra in <i>UBQLN2</i>-linked ALS/FTD but not sporadic ALS. Curiously, the striatum harboured small punctate ubiquilin 2 aggregates in all cases examined, while large diffuse striatal ubiquilin 2 aggregates were specific to <i>UBQLN2</i>-linked ALS/FTD. Overall, ubiquilin 2 is mainly deposited in clinically unaffected regions throughout the CNS such that symptomology in <i>UBQLN2</i>-linked cases maps best to the aggregation of TDP-43.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138796964","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":"Society News","authors":"","doi":"10.1111/bpa.13227","DOIUrl":"https://doi.org/10.1111/bpa.13227","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564798","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}