Free neuropathology最新文献

{"title":"Molecular fragment characteristics and distribution of tangle associated TDP-43 (TATs) and other TDP-43 lesions in Alzheimer's disease.","authors":"Keith A Josephs, Shunsuke Koga, Nirubol Tosakulwong, Stephen D Weigand, Trang Thu Nha Pham, Matt Baker, Jennifer L Whitwell, Rosa Rademakers, Leonard Petrucelli, Dennis W Dickson","doi":"10.17879/freeneuropathology-2023-5192","DOIUrl":"10.17879/freeneuropathology-2023-5192","url":null,"abstract":"<p><p>TAR DNA binding protein 43 (TDP-43) pathology is a defining feature of frontotemporal lobar degeneration (FTLD). In FTLD-TDP there is a moderate-to-high burden of morphologically distinctive TDP-43 immunoreactive inclusions distributed throughout the brain. In Alzheimer's disease (AD), similar TDP-43 immunoreactive inclusions are observed. In AD, however, there is a unique phenomenon of neurofibrillary tangle-associated TDP-43 (TATs) whereby TDP-43 intermingles with neurofibrillary tangles. Little is known about the characteristics and distribution of TATs, or how burden and distribution of TATs compares to burden and distribution of other FTLD-TDP-like lesions observed in AD. Here we characterize molecular fragment characteristics, burden and distribution of TATs and assess how these features compare to features of other TDP-43 lesions. We performed TDP-43 immunohistochemistry with anti-phosphorylated, C- and N-terminal TDP-43 antibodies in 20 high-probability AD cases and semi-quantitative burden of seven inclusion types within five brain regions (entorhinal cortex, subiculum, CA1 and dentate gyrus of hippocampus, occipitotemporal cortex). Hierarchical cluster analysis was used to analyze the dataset that consisted of 75 different combinations of neuropathological features. TATs were nonspherical with heterogeneous staining patterns and present in all regions except hippocampal dentate. All three antibodies detected TATs although N-terminal antibody sensitivity was low. Three clusters were identified: Cluster-1 had mild-moderate TATs, moderate-frequent neuronal cytoplasmic inclusions, dystrophic neurites, neuronal intranuclear inclusions and fine neurites, and perivascular and granular inclusions identified only with the N-terminal antibody throughout the brain; Cluster-2 had scant TATs in limbic regions and Cluster-3 mild-moderate TATs and mild-moderate neuronal cytoplasmic inclusions and dystrophic neurites throughout the brain and moderate fine neurites. Only 17% of cluster 1 cases had the <i>TMEM106b GG</i> (protective) haplotype and 83% had hippocampal sclerosis. Both features differed across clusters (p=0.03 & p=0.01). TATs have molecular characteristics, distribution and burden, and genetic and pathologic associations like FTLD-TDP lesions.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How and why I fell into neuropathology.","authors":"Jean Jacques Hauw","doi":"10.17879/freeneuropathology-2023-5112","DOIUrl":"10.17879/freeneuropathology-2023-5112","url":null,"abstract":"<p><p>I'm going to explain how and why I fell into the Department of Neuropathology at the Pitié-Salpêtrière Hospital of Paris. I'd also like to sketch the history of French neuropathology in the years 1960-2010, as seen by a naive young student, and then by a practicing neuropathologist (often still very naive). As a matter of fact, although the history of neurosciences [1-2] and the Pitié-Salpêtrière Hospital in Paris [3-4] have been the subject of numerous publications, the history of neuropathology in this hospital has been rarely documented [5-6]. I spent more than forty years strolling along the alleys of La Salpêtrière, among its old pavilions, the Saint Louis chapel, the \"Pavillon des folles\", the courtyard of Manon Lescaut and the guard room. I worked full-time between the Escourolle laboratory, the \"Amphithéâtre des morts\" and the University. It has been a real pleasure to be part of this world. I would also like to offer young doctors in training and future neuropathologists some advice that might help them in the choice and development of their future careers.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"63rd Annual Meeting of the Canadian Association of Neuropathologists - Association canadienne des neuropathologistes (CANP-ACNP): October 18th-21st 2023 Montreal, QC.","authors":"","doi":"10.17879/freeneuropathology-2023-5195","DOIUrl":"10.17879/freeneuropathology-2023-5195","url":null,"abstract":"<p><p>The Canadian Association of Neuropathologists - Association canadienne des neuropathologistes (CANP-ACNP) held their 63^rd annual meeting at the McGill Faculty Club and The Montreal Neurological Institute in Montreal, QC, from October 18^th to 21^st, 2023, under the leadership of Dr. Robert Hammond, President of the CANP-ACNP, Dr. Peter Schutz, Secretary Treasurer of the CANP-ACNP, and with technical support from CANP administrator Colleen Fifield. The academic program comprised 18 scientific abstracts, 14 unknown cases, a mini-symposium on molecular testing of brain tumours in Canada, and the Presidential symposium on Pediatric Neuropathology. Digital pathology images from the 14 unknown cases are available for viewing online (www.canp.ca). The unknown case sessions were moderated by Dr. Peter Schutz. The Presidential Symposium 2023 on Pediatric Neuropathology featured the Gordon Mathieson Lecture given by Dr. M. Del Bigio on in-utero infections and their effects on the developing brain, and the David Robertson Lecture given by Dr. D. van Essen entitled <i>Models and Mechanisms of Cerebral Cortical Expansion and Folding</i>. The program was completed by three invited presentations with Dr. M. Oskoui presenting on the epidemiology of cerebral palsy in Canada, Dr. P. Ballabh presenting on <i>Cerebral Gray Matter Injuries in Infants with Intraventricular Hemorrhage</i>, and Dr. W. Foulkes presenting on <i>CNS Manifestations of Dicer-1 Tumour Predisposition Syndrome</i>. The Mary Tom Award for best clinical science presentation by a trainee went to Dr. K. C. Martin (Supervisor Dr. S. Yip), and the Morrison H. Finlayson Award for best basic science presentation by a trainee was won by Dr. R. Cotau (Supervisor Dr. M. Richer). The following abstracts were presented at the 63^rd annual meeting of the Canadian Association of Neuropathologists - Association candienne des neuropathologistes (CANP-ACNP) in October 2023.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference on copy number variations in pleomorphic xanthoastrocytoma: Implications for diagnostic approach.","authors":"David E Reuss, Daniel Schrimpf, Damian Stichel, Azadeh Ebrahimi, Chris Dampier, Kenneth Aldape, Matija Snuderl, David Capper, Martin Sill, David T W Jones, Stefan M Pfister, Felix Sahm, Andreas von Deimling","doi":"10.17879/freeneuropathology-2023-5156","DOIUrl":"10.17879/freeneuropathology-2023-5156","url":null,"abstract":"<p><p>Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic challenge. The present study relies on methylation-based predictions and focuses on copy number variations (CNV) in PXA. We identified 551 tumors from patients having received the histologic diagnosis or differential diagnosis pleomorphic xanthoastrocytoma (PXA) uploaded to the web page www.molecularneuropathology.org. Of these 551 tumors, 165 received the prediction \"methylation class (anaplastic) pleomorphic xanthoastrocytoma\" with a calibrated score >=0.9 by the brain tumor classifier version v12.8 and, therefore, were defined the PXA reference set designated mcPXAref. In addition to these 165 mcPXAref, 767 other tumors received the prediction mcPXA with a calibrated score >=0.9 but without a histological PXA diagnosis. The total number of individual tumors predicted by histology and/or by methylome based classification as PXA, mcPXA or both was 1318, and these were designated the study cohort. The selection of a control cohort was guided by methylation-based predictions recurrently observed for the other 386/551 tumors diagnosed as histologic PXA. 131/386 received predictions for another entity besides PXA with a score >=0.9. Control tumors corresponding to the 11 most common other predictions were selected, adding up to 1100 reference cases. CNV profiles were calculated from all methylation datasets of the study and control cohorts. Special attention was given to the 7/10 signature, gene amplifications and homozygous deletion of CDKN2A/B. Comparison of CNV in the subsets of the study cohort and the control cohort were used to establish relations independent of histological diagnoses. Tumors in mcPXA were highly homogenous in regard to CNV alterations, irrespective of the histological diagnoses. The 7/10 signature commonly present in glioblastoma, IDH-wildtype, was present in 15-20% of mcPXA, whereas amplification of oncogenes (likewise common in glioblastoma) was very rare in mcPXA (<1%). In contrast, the histology-based PXA group exhibited high variance in regard to methylation classes as well as to CNVs. Our data add to the notion, that histologically defined PXA likely only represent a subset of the biological disease.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A historical look using virtual microscopy: the first case report of adrenomyeloneuropathy (AMN).","authors":"Herbert Budka","doi":"10.17879/freeneuropathology-2023-5115","DOIUrl":"10.17879/freeneuropathology-2023-5115","url":null,"abstract":"<p><p>The history of adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) and other peroxisomal diseases is exemplary for the stunning progress of scientific medicine within the past 50 years. Like many breakthroughs in medicine, the detailed analysis of patients' pathologically affected tissues was instrumental, resulting in stepwise systematic clarification of what had remained enigmatic until the 1970s. This flashback paper is a recollection of the first neuropathological description of a slowly evolving clinical phenotype, spastic paraparesis with adrenal insufficiency, in a young adult by Budka et al. 1976 [3], using virtual microscopy of the original histologic slides. The clinico-pathological presentation derives from the classical cerebral ALD phenotype in boys, where electron microscopy demonstrated the underlying pathological hallmark of characteristic lipid inclusions shared by both phenotypes. Our report allowed the delineation of a new disease type almost simultaneously described in more cases as AMN by Griffin et al. 1977 [4] and Schaumburg et al. 1977 [11]. Moreover, our report indicated clinical heterogeneity in the ALD disease group that, as shown later, extends further to females, to Addison-only, and even to asymptomatic subjects. The gene underlying ALD was discovered in 1993 as a defect in the <i>ABCD1</i> gene. Yet, it has hitherto remained unclear how the gene defect causes the strikingly broad and unpredictable phenotypic spectrum of ALD/AMN.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71432299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological perspectives in pilocytic astrocytomas: Extent of resection as the sole critical factor for recurrence-free survival, and the challenge of evaluating conclusions derived from limited data.","authors":"Ibrahim Kulac, Irem Yenidogan, Banu Oflaz Sozmen, Arzu Baygul, Soonmee Cha, Melike Pekmezci, Tarik Tihan","doi":"10.17879/freeneuropathology-2023-5116","DOIUrl":"10.17879/freeneuropathology-2023-5116","url":null,"abstract":"<p><p><b>Introduction:</b> Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. <b>Materials and Methods:</b> We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. <b>Results:</b> Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p <0.001). <b>Conclusion:</b> Multivariate analysis was able to identify extent of resection as the only significant variable to influence recurrence-free survival. We did not find a statistically significant association between age, <i>NF1</i> status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"My recollections of my 50 years as a neuropathologist from a neurologist's perspective.","authors":"Yoshio Hashizume","doi":"10.17879/freeneuropathology-2023-5108","DOIUrl":"10.17879/freeneuropathology-2023-5108","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586208/pdf/freeneuropathol-04-16-5018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum neurofilament light chains in progressive multiple sclerosis patients treated with repeated cycles of high-dose intravenous steroids.","authors":"Lidia Stork, Michael Haupts, Niels Kruse, Petra Spill-Askeridis, Adriane Kutllovci, Martin S Weber, Wolfgang Brück, Imke Metz","doi":"10.17879/freeneuropathology-2023-5049","DOIUrl":"10.17879/freeneuropathology-2023-5049","url":null,"abstract":"<p><p><b>Background and objectives:</b> In progressive multiple sclerosis (MS) patients, CNS inflammation trapped behind a closed blood brain barrier drives continuous neuroaxonal degeneration, thus leading to deterioration of neurological function. Therapeutics in progressive MS are limited. High-dose intravenous glucocorticosteroids (HDCS) can cross the blood-brain barrier and may reduce inflammation within the CNS. However, the treatment efficacy of HDCS in progressive MS remains controversial. Serum neurofilament light chains (sNfL) are an established biomarker of neuroaxonal degeneration and are used to monitor treatment responses. We aimed to investigate whether repeated cycles of intravenous HDCS reduce the level of sNfL in progressive MS patients. <b>Methods:</b> We performed a monocentric observational study of 25 patients recruited during ongoing clinical routine care who were treated with repeated cycles of intravenous HDCS as long-term therapy for their progressive MS. sNfL were measured in 103 repeated blood samples (median time interval from baseline 28 weeks, range 2-55 weeks) with the Single Molecular Array (SiMoA) technology. The Expanded Disability Status Score (EDSS) was documented at baseline and follow-up. <b>Results:</b> The median age of patients was 55 years (range 46-77 years) with a median disease duration of 26 years (range 11-42 years). sNfL baseline levels at study inclusion were significantly higher in progressive MS patients compared to age-matched healthy controls (median 16.7 pg/ml vs 11.5 pg/ml, p=0.002). sNfL levels showed a positive correlation with patient age (r=0.2, p=0.003). The majority of patients (72%, 16/23) showed reduced sNfL levels ≥20 weeks after HDCS compared to baseline (median 13.3 pg/ml, p=0.03). sNfL levels correlated negatively with the time interval from baseline HDCS therapy (r=-0.2, p=0.03). This association was also evident after correction for treatment with disease-modifying drugs (adjusted R²=0.10, p=0.001). The EDSS remained stable (median 6.5) within a median treatment duration of 26 weeks (range 13-51 weeks). <b>Conclusion:</b> Although larger studies are needed to confirm our findings, we were able to demonstrate that HDCS treatment reduces sNfL levels and therefore may slow down neuroaxonal damage in a subgroup of patients with progressive MS. Moreover, a stable EDSS was observed during therapy. Findings suggest that HDCS may be beneficial for the treatment of progressive MS.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583007/pdf/freeneuropathol-04-15-5049.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotrauma: 2023 Update.","authors":"David S Priemer, Daniel P Perl","doi":"10.17879/freeneuropathology-2023-5076","DOIUrl":"10.17879/freeneuropathology-2023-5076","url":null,"abstract":"<p><p>2022 was a productive year for research in traumatic brain injury (TBI) and resultant neuropathology. After an extensive review, we present related studies and publications which we felt were of particular importance to the neuropathology community. First, 2022 was highlighted by important advancements in the diagnosis and, moreover, our understanding of chronic traumatic encephalopathy (CTE). Important publications include a pair concluding that CTE primarily concerns neuronal accumulation of phosphorylated tau (<i>ptau</i>), but that glial <i>ptau</i> accumulation often helps to facilitate diagnosis. In addition, a new large community study from Australia continues the indication that CTE is relatively uncommon in the community, and the first large-cohort study on brains of military personnel similarly demonstrates that CTE appears to be uncommon among service members and does not appear to explain high rates of neuropsychiatric sequelae suffered by the warfighter. The causation of CTE by impact-type TBI was supported by the application of the Bradford Hill criteria, within the brains of headbutting bovids, and interestingly within an artificial head model exposed to linear impact. Finally, a large-scale analysis of <i>APOE</i> genotypes contends that gene status may influence CTE pathology and outcomes. In experimental animal work, a study using mouse models provided important evidence that TDP-43 facilitates neurodegenerative pathology and is implicated in cognitive dysfunction following TBI, and another study using a swine model for concussion demonstrated that evidence that axonal sodium channel disruption may be a driver of neurologic dysfunction after concussion. Finally, we end with memoriam to Dr. John Q. Trojanowski, a giant of neurodegenerative research and an important contributor to the neurotrauma literature, who we lost in 2022.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510742/pdf/freeneuropathol-04-14-5076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration: 2023 update.","authors":"John F Crary","doi":"10.17879/freeneuropathology-2023-4899","DOIUrl":"10.17879/freeneuropathology-2023-4899","url":null,"abstract":"<p><p>This paper reviews ten highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As in previous years, the focus is to highlight human tissue-based experimentation most relevant to neuropathologists. A concerted effort was made to balance the selected studies across disease categories, approaches, and methodologies to capture the breadth of the research landscape. Studies include an integrated proteomic and transcriptomic study of Alzheimer disease (AD) and new consensus diagnostic neuropathological criteria for progressive supranuclear palsy. A number of studies looking at TAR DNA-binding protein 43 (TDP-43) are highlighted. One examined interaction between AD and limbic age-related TDP-43 encephalopathy (LATE) and yet another demonstrated how TDP-43 represses cryptic exon inclusion in <i>UNC13A</i>, suggesting a novel pathogenic mechanism. Most surprisingly, three cryogenic electron microscopy (cryo-EM) studies showed that <i>TMEM106B</i> filaments form the core of TDP-43-positive inclusions. Cryo-EM revealed a prion protein amyloid structure from aggregates in Gerstmann-Sträussler-Scheinker disease. There was an elegant functional genomic study cataloging microglial gene expression in the human brain. A study shed light on how <i>APOE</i> influences chronic traumatic encephalopathy. A pathoanatomical study tested the dual hit hypothesis of Lewy body progression throughout the nervous system. And finally, deep learning continues to show its promise with application of a weakly supervised multiple instance learning paradigm to assess aging post-mortem brains.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484115/pdf/freeneuropathol-04-13-4899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10225723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}