Brain Pathology最新文献

{"title":"A mass in the pineal region of a young woman","authors":"Lorraina J. Robinson, Eric Goold, David Anderson, Robert C. Rennert, William T. Couldwell, Changhong Xing","doi":"10.1111/bpa.13258","DOIUrl":"10.1111/bpa.13258","url":null,"abstract":"<p>This case involves an 18-year-old female with no significant past medical history who was found to have a large pineal and third ventricular tumor with obstructive hydrocephalus after experiencing subacute, progressive headaches, and an acute episode of sudden vision loss. She underwent a ventriculoperitoneal shunt at an outside facility with improvement in her vision before presenting as a transfer to our facility. Brain magnetic resonance imaging upon transfer demonstrated a large, heterogenous enhancing mass (6.6 × 6.1 × 5.7 cm) centered in the pineal region with extension into the third and right lateral ventricles (Figure 1). The tumor exerted mass effect by splaying the bilateral thalami with effacement of the basal cisterna, effacement of the cerebral aqueduct, and an 8 mm tonsillar herniation. Surgery was pursued for a definitive diagnosis and tumor debulking. Intraoperatively, the tumor demonstrated variable soft and firm consistency with moderate vascularity. Post-operative imaging did not demonstrate clear residual tumor. She was discharged with no new neurologic deficits.</p><p>Histology of H&E-stained sections demonstrated a moderately hypercellular neoplasm consisting of an admixture of small to medium-sized spindle cells embedded in a heavily collagenized and myxoid matrix (Box 1, Figure 2A, B). Tumor cells were observed forming disorganized, haphazard architectural patterns while some tumor cells were seen floating in a loose basophilic myxoid matrix (Figure 2A). The mitotic index was <1/10 high-power-fields. Necrosis was absent. By immunohistochemistry, the tumor cells were patchy positive for CD163 (Figure 2C) and CD99 (Figure 2D), focally positive for desmin (Figure 2D inset), and negative for GFAP, OLIG2, CD34, and SSTR2. MIB-1 proliferation index was overall low (1%–2%) (Figure 2E) but focally increased at approximately 10% (Figure 2E inset). Immunostaining for SMARCB1 showed loss of expression in many of the tumor cells (Figure 2F).</p><p>NeoTYPE brain tumor profile (DNA and RNA) from NeoGenomics was performed, and no pathogenic mutations or fusions were detected. However, a variant of unknown clinical significance involving the <i>SMARCB1</i> gene c.91G>A (p.Glu31Lys) E31K NM_003073.5:c.91G>A was detected. Whole genome methylation profiling was performed at the National Institute of Health (NIH)/National Cancer Institute (NCI) for confirmation of the diagnosis. The composite NIH/NCI methylation profile classified the tumor with a high confidence score (0.99) as a desmoplastic myxoid tumor, <i>SMARCB1</i>-altered.</p><p>Desmoplastic myxoid tumor (DMT) of the pineal region, <i>SMARCB1</i>-mutant.</p><p>As defined by the most recent 2021 World Health Organization (WHO) Central Nervous System tumor classification, DMT of the pineal region, <i>SMARCB1</i>-mutant, maintains a unique <i>SMARCB1</i>-mutation while histologically displaying desmoplasia and myxoid changes but lacking histopathological signs of maligna","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288275","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":"NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors","authors":"Kathryn L. Eschbacher,&nbsp;Quynh T. Tran,&nbsp;Evgeny A. Moskalev,&nbsp;Sarah Jenkins,&nbsp;Karen Fritchie,&nbsp;Robert Stoehr,&nbsp;Alissa Caron,&nbsp;Michael J. Link,&nbsp;Paul D. Brown,&nbsp;Andrew Guajardo,&nbsp;Daniel J. Brat,&nbsp;Ashley Wu,&nbsp;Sandro Santagata,&nbsp;David N. Louis,&nbsp;Priscilla K. Brastianos,&nbsp;Alexander B. Kaplan,&nbsp;Brian Alexander,&nbsp;Sabrina Rossi,&nbsp;Fabio Ferrarese,&nbsp;David R. Raleigh,&nbsp;Minh P. Nguyen,&nbsp;John Gross,&nbsp;Jose Velazquez Vega,&nbsp;Fausto Rodriguez,&nbsp;Arie Perry,&nbsp;Maria Martinez-Lage,&nbsp;Brent A. Orr,&nbsp;Florian Haller,&nbsp;Caterina Giannini","doi":"10.1111/bpa.13256","DOIUrl":"10.1111/bpa.13256","url":null,"abstract":"<p>Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days–43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (<i>n</i> = 80) and targeted <i>TERT</i> promoter mutation testing (<i>n</i> = 98). Associations were examined with <i>NAB2::STAT6</i> fusion status (<i>n</i> = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. <i>NAB2::STAT6</i> fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (<i>p</i> = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (<i>p</i> = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (<i>n</i> = 38), Cluster 2 (<i>n</i> = 22), and Cluster 3 (<i>n</i> = 20). Methylation clusters were significantly associated with fusion type (<i>p</i> &lt; 0.001), with Cluster 2 harboring ex4::ex2-3 fusion in 16 (of 20; 80.0%), nearly all <i>TERT</i> promoter mutations (7 of 8; 87.5%), and predominantly an “SFT” histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5-7::ex16-17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (<i>p</i> = 0.027), but not overall survival (OS). In summary, <i>NAB2::STAT6</i> fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16-17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, <i>TERT</i> promoter mutation status, histologic phenotype, and MFS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206382","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":"Oligodendrocyte progenitor cells' fate after neonatal asphyxia—Puzzling implications for the development of hypoxic–ischemic encephalopathy","authors":"Justyna Janowska,&nbsp;Justyna Gargas,&nbsp;Karolina Zajdel,&nbsp;Michal Wieteska,&nbsp;Kamil Lipinski,&nbsp;Malgorzata Ziemka-Nalecz,&nbsp;Malgorzata Frontczak-Baniewicz,&nbsp;Joanna Sypecka","doi":"10.1111/bpa.13255","DOIUrl":"10.1111/bpa.13255","url":null,"abstract":"<p>Premature birth or complications during labor can cause temporary disruption of cerebral blood flow, often followed by long-term disturbances in brain development called hypoxic–ischemic (HI) encephalopathy. Diffuse damage to the white matter is the most frequently detected pathology in this condition. We hypothesized that oligodendrocyte progenitor cell (OPC) differentiation disturbed by mild neonatal asphyxia may affect the viability, maturation, and physiological functioning of oligodendrocytes. To address this issue, we studied the effect of temporal HI in the in vivo model in P7 rats with magnetic resonance imaging (MRI), microscopy techniques and biochemical analyses. Moreover, we recreated the injury in vitro performing the procedure of oxygen–glucose deprivation on rat neonatal OPCs to determine its effect on cell viability, proliferation, and differentiation. In the in vivo model, MRI evaluation revealed changes in the volume of different brain regions, as well as changes in the directional diffusivity of water in brain tissue that may suggest pathological changes to myelinated neuronal fibers. Hypomyelination was observed in the cortex, striatum, and CA3 region of the hippocampus. Severe changes to myelin ultrastructure were observed, including delamination of myelin sheets. Interestingly, shortly after the injury, an increase in oligodendrocyte proliferation was observed, followed by an overproduction of myelin proteins 4 weeks after HI. Results verified with the in vitro model indicate, that in the first days after damage, OPCs do not show reduced viability, intensively proliferate, and overexpress myelin proteins and oligodendrocyte-specific transcription factors. In conclusion, despite the increase in oligodendrocyte proliferation and myelin protein expression after HI, the production of functional myelin sheaths in brain tissue is impaired. Presented study provides a detailed description of oligodendrocyte pathophysiology developed in an effect of HI injury, resulting in an altered CNS myelination. The described models may serve as useful tools for searching and testing effective of effective myelination-supporting therapies for HI injuries.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166088","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":"Dysregulation of the renin-angiotensin system in vascular dementia","authors":"H. M. Tayler,&nbsp;O. A. Skrobot,&nbsp;D. H. Baron,&nbsp;P. G. Kehoe,&nbsp;J. S. Miners","doi":"10.1111/bpa.13251","DOIUrl":"10.1111/bpa.13251","url":null,"abstract":"<p>The renin-angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (<i>n</i> = 42), Alzheimer's disease (<i>n</i> = 50), mixed AD/VaD (<i>n</i> = 50) and age-matched controls (<i>n</i> = 50). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE-1 and ACE-2 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang-II, Ang-III and Ang-(1–7)) levels were measured by ELISA. ACE-1 protein level and enzyme activity, and Ang-II and Ang-III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE-1 and Ang-II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE-2 level was elevated in frontal white matter in vascular dementia. Ang-(1–7) level was elevated across all dementia groups compared to age-matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE-1 protein was reduced and ACE-2 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058728","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":"Neuropathological stage-dependent proteome mapping of the olfactory tract in Alzheimer's disease: From early olfactory-related omics signatures to computational repurposing of drug candidates","authors":"Paz Cartas-Cejudo,&nbsp;Adriana Cortés,&nbsp;Mercedes Lachén-Montes,&nbsp;Elena Anaya-Cubero,&nbsp;Elena Puerta,&nbsp;Maite Solas,&nbsp;Joaquín Fernández-Irigoyen,&nbsp;Enrique Santamaría","doi":"10.1111/bpa.13252","DOIUrl":"10.1111/bpa.13252","url":null,"abstract":"<p>Alzheimer's disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss, and behavioral deterioration. Albeit substantial progress has been made in characterizing AD-associated molecular and cellular events, there is an unmet clinical need for new therapies. In this study, olfactory tract proteotyping performed in controls and AD subjects (<i>n</i> = 17/group) showed a Braak stage-dependent proteostatic impairment accompanied by the progressive modulation of amyloid precursor protein and tau functional interactomes. To implement a computational repurposing of drug candidates with the capacity to reverse early AD-related olfactory omics signatures (OMSs), we generated a consensual OMSs database compiling differential omics datasets obtained by mass-spectrometry or RNA-sequencing derived from initial AD across the olfactory axis. Using the Connectivity Map-based drug repurposing approach, PKC, EGFR, Aurora kinase, Glycogen synthase kinase, and CDK inhibitors were the top pharmacologic classes capable to restore multiple OMSs, whereas compounds with targeted activity to inhibit PI3K, Insulin-like growth factor 1 (IGF-1), microtubules, and Polo-like kinase (PLK) represented a family of drugs with detrimental potential to induce olfactory AD-associated gene expression changes. To validate the potential therapeutic effects of the proposed drugs, in vitro assays were performed. These validation experiments revealed that pretreatment of human neuron-like SH-SY5Y cells with the EGFR inhibitor AG-1478 showed a neuroprotective effect against hydrogen peroxide-induced damage while the pretreatment with the Aurora kinase inhibitor Reversine reduced amyloid-beta (Aβ)-induced neurotoxicity. Taken together, our data pointed out that OMSs may be useful as substrates for drug repurposing to propose novel neuroprotective treatments against AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058729","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":"Astrocytic phagocytosis in the medial prefrontal cortex jeopardises postoperative memory consolidation in mice","authors":"Xin Ma,&nbsp;Yuan Le,&nbsp;Lin Hu,&nbsp;Wen Ouyang,&nbsp;Cheng Li,&nbsp;Daqing Ma,&nbsp;Jianbin Tong","doi":"10.1111/bpa.13253","DOIUrl":"10.1111/bpa.13253","url":null,"abstract":"<p>Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep-Sev-stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)-dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV-GFAP-hM4Di-eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co-labelling hippocampal neuronal axon terminals with PSD-95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep-Sev-stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, <i>p</i> = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, <i>p</i> = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, <i>p</i> = 0.001) in mice when compared with these in the naïve controls. Hep-Sev-stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional-dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep-Sev-stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis-induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058727","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":"Meeting report of the 20th International Congress of Neuropathology (ICN) 2023 in Berlin","authors":"Hans H. Goebel,&nbsp;Arend Koch,&nbsp;Helena Radbruch,&nbsp;Simone Schmid,&nbsp;Ekaterina Friebel,&nbsp;Werner Stenzel,&nbsp;Frank L. Heppner,&nbsp;David Capper","doi":"10.1111/bpa.13249","DOIUrl":"10.1111/bpa.13249","url":null,"abstract":"&lt;p&gt;Exactly 62 years to the month after the 4th International Congress of Neuropathology (ICN) took place from September 4th to 8th 1961 at the Ludwig Maximilian University of Munich, the global neuropathological community—or, more accurately, its neuropathological children and grandchildren—returned back to the 20th ICN, that is, ICN2023, in Berlin/Germany (12–16 September 2023).&lt;/p&gt;&lt;p&gt;The archives of the International Society of Neuropathology (ISN), gainfully groomed by Maria Thom at University College, London/UK, provided extensive information on the scope, frame, and content of the earlier Munich ICN, which enabled a quick and insightful glimpse into the evolution of ICN between these two events, then and now.&lt;/p&gt;&lt;p&gt;In 1961, the documents of the 4th ICN were primarily produced in German and only secondly in English. Abstracts could only be submitted for oral presentations, as posters had not been “invented” but the submission languages were quite diverse, with abstracts in English, German, French, Italian, and Spanish. However, whether the multilingual presentations were delivered in the language as their titles suggested, remains unknown. Around 230 presentations were listed in the program and were held in two parallel sessions covering main topics according to different methodological techniques: “Histochemistry,” “Electron microscopy” and “Tissue culture” as well as “Free Communication” the entire content of which was subsequently published as “Proceedings” by Thieme Publishing Company [&lt;span&gt;1&lt;/span&gt;]. The President of the International Committee of Neuropathology, Webb Haymaker from the United States, delivered a lengthy and solemn welcome opening address, presenting “perspectives on Neuropathology.” Following this, the local organizer and host of ICN1961, Willibald Scholz from Munich/Germany, and Hans Jacob, the General Secretary of ICN1961 from Marburg/Germany, addressed the audience. Recognition and merit awards were then presented to Armano Ferraro from New York City and Ludo van Bogaert from Antwerp. The presumably quite elaborate opening ceremony of ICN1961 was commented with a handwritten “Amen” in the archival papers by an unidentified critical reader. Two exhibitions, one with neuropathological slides and photographs, one with historical aspects of German Neuropathology, completed the scientific part of ICN1961. Socially, the participants were feasted to receptions hosted by the Bavarian State Government, the Mayor of Munich, a special opera performance of “Cosi fan tutte” at the Cuvillies Theater, and a gala banquet at the luxury hotel “Bayerischer Hof,” for a $15/20 registration fee and $5 for the banquet. A separate “Ladies' Program” encompassed a city tour, a visit to an antique collection, and a day tour to the tourist attraction “Wies-Kirche.” Finally, a post congress trip via Venice to the International Congress of Neurology in Rome was offered.&lt;/p&gt;&lt;p&gt;In 2016, at the European Congress of Neuropathology in Bordeaux, France","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989346","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":"Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights","authors":"Sergio Pérez-Oliveira,&nbsp;Juan Castilla-Silgado,&nbsp;Cèlia Painous,&nbsp;Iban Aldecoa,&nbsp;Manuel Menéndez-González,&nbsp;Marta Blázquez-Estrada,&nbsp;Daniela Corte,&nbsp;Cristina Tomás-Zapico,&nbsp;Yaroslau Compta,&nbsp;Esteban Muñoz,&nbsp;Albert Lladó,&nbsp;Mircea Balasa,&nbsp;Gemma Aragonès,&nbsp;Pablo García-González,&nbsp;Maitée Rosende-Roca,&nbsp;Mercè Boada,&nbsp;Agustín Ruíz,&nbsp;Pau Pastor,&nbsp;Beatriz De la Casa-Fages,&nbsp;Alberto Rabano,&nbsp;Raquel Sánchez-Valle,&nbsp;Laura Molina-Porcel,&nbsp;Victoria Álvarez","doi":"10.1111/bpa.13250","DOIUrl":"10.1111/bpa.13250","url":null,"abstract":"<p>Previous studies have suggested a relationship between the number of CAG triplet repeats in the <i>HTT</i> gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of <i>HTT</i> is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the <i>HTT</i> gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (<i>n</i>=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological <i>HTT</i> expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the <i>HTT</i> CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between <i>HTT</i> CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for <i>HTT</i> repeat expansions should be considered in tauopathies.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989345","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.13241","DOIUrl":"https://doi.org/10.1111/bpa.13241","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139993955","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":"Ranking and filtering of neuropathology features in the machine learning evaluation of dementia studies","authors":"Mohammed D. Rajab,&nbsp;Teruka Taketa,&nbsp;Stephen B. Wharton,&nbsp;Dennis Wang,&nbsp;Cognitive Function and Ageing Neuropathology Study, and for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1111/bpa.13247","DOIUrl":"10.1111/bpa.13247","url":null,"abstract":"<p>Early diagnosis of dementia diseases, such as Alzheimer's disease, is difficult because of the time and resources needed to perform neuropsychological and pathological assessments. Given the increasing use of machine learning methods to evaluate neuropathology features in the brains of dementia patients, it is important to investigate how the selection of features may be impacted and which features are most important for the classification of dementia. We objectively assessed neuropathology features using machine learning techniques for filtering features in two independent ageing cohorts, the Cognitive Function and Aging Studies (CFAS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). The reliefF and least loss methods were most consistent with their rankings between ADNI and CFAS; however, reliefF was most biassed by feature–feature correlations. Braak stage was consistently the highest ranked feature and its ranking was not correlated with other features, highlighting its unique importance. Using a smaller set of highly ranked features, rather than all features, can achieve a similar or better dementia classification performance in CFAS (60%–70% accuracy with Naïve Bayes). This study showed that specific neuropathology features can be prioritised by feature filtering methods, but they are impacted by feature–feature correlations and their results can vary between cohort studies. By understanding these biases, we can reduce discrepancies in feature ranking and identify a minimal set of features needed for accurate classification of dementia.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905138","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}