Brain Pathology最新文献

{"title":"Multiple intra-axial lesions in a 57-year-old male with a history of B-cell chronic lymphocytic leukemia","authors":"Sofia Asioli, Lina Cardisciani, Matteo Martinoni, Caterina Tonon, Rocco Liguori, Pierluigi Zinzani, Luisa Di Sciascio, Elena Sabattini","doi":"10.1111/bpa.13296","DOIUrl":"10.1111/bpa.13296","url":null,"abstract":"<p>A 57-year-old male with a recent history of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (BCLL/SLL), developed a persistent left-frontal headache. One month after the onset of headache and 2 days after the second dose of anti-SARS-CoV2 mRNA vaccine, he developed a persistent high fever. He was monitored for the following days and 20 days later, he experienced tonic–clonic seizures with post-critical coma (Day 1). CT and MRI scans showed multiple sub and supra-tentorial intra-axial edematous lesions with contrast enhancement and without mass effect, as shown in Figure 1. He started dexamethasone and levetiracetam with subsequent total recovery of vigilance on Day 3 (Box 1).</p><p>On Day 6, a stereotactic biopsy of the major frontal lesion showed the presence of necrotic tissue. Following clinical improvement, on Day 9 he was discharged, with dexamethasone taping from Day 20. On Day 40 a control RMI showed edema reduction, but new nodules appeared. He was admitted again and underwent CSF analysis, lymphocyte characterization, blood culture, and total body <sup>18</sup>FDG-PET-CT, all non-contributive.</p><p>Still, under steroid tapering, the patient became unresponsive and febrile again, so corticosteroid dosing was increased. After initial improvement he went into hyponatremic coma, consistent with inappropriate ADH secretion syndrome. A new MRI showed a further increase in the lesions and expanded edema. On Day 67 a new open biopsy of the left frontal lesion was performed. After histologic diagnosis, the patient was referred to the Onco-Hematology department where a bone marrow biopsy confirmed a modest infiltration by BCLL/SLL (10% of cellularity). Chemotherapy with MATRix regimen was started with only mild improvement. He ultimately succumbed to the disease on Day 98.</p><p>On hematoxylin–eosin the lesion showed extensive necrosis with predominantly medium-sized, atypical lymphoid cells with irregular nuclei, moderate amount of pale cytoplasm with vascular proliferation and histiocytic elements (Figure 2A–C). The neoplastic cells displayed angiocentric growth, mitoses, and apoptotic bodies. CD3 (Figure 2D) and CD2 were positive in neoplastic cells (Figure 2E) as well as Beta-F1 for the αβ T-cell receptor (TCR) dimer; CD20, PAX5, CD5, CD7, CD4, CD8, TdT, CD56, Tia-1, and TCR-γ dimer were negative. Epstein–Barr virus-encoded small RNAs were not detected at in situ hybridization. TCR Gamma rearrangement (TRG) was analyzed by GeneScanning and two distinct reproducible peaks were detected (Figure 2E) interpreted as either a biallelic or biclonal rearrangement.</p><p>Peripheral T cell lymphoma, Not Otherwise Specified (NOS) consistent with Primary CNS T cell lymphoma.</p><p>Peripheral T-cell lymphoma (PTCLs) accounts for 2%–4% of primary CNS lymphomas in Europe. Immunodeficiency might play a role in the etiology of the disease in a subset of patients. Involved sites include the frontal and temporal lobes, cerebellum, pituitary, a","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900937","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":"Microtubule-associated NAV3 regulates invasive phenotypes in glioblastoma cells.","authors":"Aneta Škarková, Markéta Pelantová, Ondřej Tolde, Anna Legátová, Rosana Mateu, Petr Bušek, Elena Garcia-Borja, Aleksi Šedo, Sandrine Etienne-Manneville, Daniel Rösel, Jan Brábek","doi":"10.1111/bpa.13294","DOIUrl":"https://doi.org/10.1111/bpa.13294","url":null,"abstract":"<p><p>Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13294"},"PeriodicalIF":5.8,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pituitary mass in a 46-year-old woman","authors":"Francesco E. Emiliani,&nbsp;Donald C. Green,&nbsp;Edward G. Hughes,&nbsp;Wahab A. Khan,&nbsp;George J. Zanazzi,&nbsp;Chun-Chieh Lin","doi":"10.1111/bpa.13295","DOIUrl":"10.1111/bpa.13295","url":null,"abstract":"&lt;p&gt;A 46-year-old woman presented to the clinic with a 6-week history of left retro-orbital headaches. In recent weeks, she had developed increased thirst, a salty taste, and diplopia with blurry vision in the left eye. On examination, left cranial nerve six palsy was noted. Magnetic resonance imaging (MRI) revealed a 2.7 cm heterogeneously enhancing pituitary mass (Figure 1). Laboratory findings showed slightly elevated prolactin (83.8 ng/mL; reference: 4.8–23.3 ng/mL). There were no other findings associated with hypo/hyperpituitarism. During transsphenoidal resection, the tumor appeared to be adherent and firm with indistinct boundary with the pituitary gland. A portion of the tumor infiltrating the cavernous sinus was left behind to prevent damage to the cavernous segment of the carotid artery.&lt;/p&gt;&lt;p&gt;Intraoperative cytological smears showed pleomorphic tumor cells with prominent nucleoli and minimal cytoplasm (Figure 2A and Box 1). Histological examination of formalin-fixed paraffin-embedded (FFPE) tissue showed a poorly differentiated neoplasm with high mitotic counts (up to five per high-power field), forming a sheet-like architecture. Tumor cells exhibited prominent nucleoli and vesicular chromatin with cytoplasmic vacuolation. Occasional intracytoplasmic globular eosinophilic inclusions were noted (Figure 2B). Immunohistochemical study showed that the tumor was negative for CK (AE1/AE3), GFAP, synaptophysin, LCA, Melan A, HMB-45, Oct3/4, PLAP, and brachyury. Notably, the tumor showed loss of nuclear SMARCB1/INI1 staining (Figure 2C). Ki67 index was elevated (70%).&lt;/p&gt;&lt;p&gt;Chromosomal microarray analysis (CMA) demonstrated copy neutral loss of heterozygosity (cnLOH) in nearly the entire chromosome 22 that includes the &lt;i&gt;SMARCB1&lt;/i&gt; locus at 22q11.2 (Figure 2D). Next-generation sequencing (NGS) detected a frameshift deletion in the 3′ end of &lt;i&gt;SMARCB1&lt;/i&gt; (p. P383Rfs c.1148del; VAF = 74.2%) (Figure 2E). No other mutation was identified. Brain tumor methylation profiling from National Cancer Institute classified this tumor as an AT/RT subclass MYC (calibrated score of 0.95).&lt;/p&gt;&lt;p&gt;Adult sellar atypical teratoid/rhabdoid tumor, CNS WHO grade 4.&lt;/p&gt;&lt;p&gt;Adult sellar AT/RT is a rare, aggressive CNS embryonal tumor, with less than 50 cases reported to date. By definition, it occurs in the sellar/suprasellar region of adults, displays variable polyphenotypic differentiation and demonstrates characteristic &lt;i&gt;SMARCB1&lt;/i&gt; mutations. Notably, there is a strong female predominance (95%) and middle age distribution (mean = 44 ± 3 years) [&lt;span&gt;1-3&lt;/span&gt; and current case]. This contrasts with pediatric AT/RT, which shows a slight male predominance and has not been reported in the sellar region.&lt;/p&gt;&lt;p&gt;On MRI, adult sellar AT/RT is frequently described as a heterogeneously enhancing pituitary mass with invasion of adjacent structures. Due to its rarity and non-specific histological findings, the differential diagnosis is usually broad [&lt;span&gt;1-3&lt;/span&gt;]. A","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874212","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":"Transmembrane and coiled-coil 2 associates with Alzheimer's disease pathology in the human brain.","authors":"Paul C R Hopkins, Claire Troakes, Andrew King, Guy Tear","doi":"10.1111/bpa.13290","DOIUrl":"https://doi.org/10.1111/bpa.13290","url":null,"abstract":"<p><p>Transmembrane and coiled-coil 2 (TMCC2) is a human orthologue of the Drosophila gene dementin, mutant alleles of which cause neurodegeneration with features of Alzheimer's disease (AD). TMCC2 and Dementin further have an evolutionarily conserved interaction with the amyloid protein precursor (APP), a protein central to AD pathogenesis. To investigate if human TMCC2 might also participate in mechanisms of neurodegeneration, we examined TMCC2 expression in late onset AD human brain and age-matched controls, familial AD cases bearing a mutation in APP Val717, and Down syndrome AD. Consistent with previous observations of complex formation between TMCC2 and APP in the rat brain, the dual immunocytochemistry of control human temporal cortex showed highly similar distributions of TMCC2 and APP. In late onset AD cases stratified by APOE genotype, TMCC2 immunoreactivity was associated with dense core senile plaques and adjacent neuronal dystrophies, but not with Aβ surrounding the core, diffuse Aβ plaques or tauopathy. In Down syndrome AD, we observed in addition TMCC2-immunoreactive and methoxy-X04-positive pathological features that were morphologically distinct from those seen in the late onset and familial AD cases, suggesting enhanced pathological alteration of TMCC2 in Down syndrome AD. At the protein level, western blots of human brain extracts revealed that human brain-derived TMCC2 exists as at least three isoforms, the relative abundance of which varied between the temporal gyrus and cerebellum and was influenced by APOE and/or dementia status. Our findings thus implicate human TMCC2 in AD via its interactions with APP, its association with dense core plaques, as well as its alteration in Down syndrome AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13290"},"PeriodicalIF":5.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The historical background of hereditary cystatin C amyloid angiopathy: Genealogical, pathological, and clinical manifestations.","authors":"Asbjorg Osk Snorradottir, Hakon Hakonarson, Astridur Palsdottir","doi":"10.1111/bpa.13291","DOIUrl":"https://doi.org/10.1111/bpa.13291","url":null,"abstract":"<p><p>Hereditary cystatin C amyloid angiopathy (HCCAA) is an Icelandic disease that belongs to a disease class called cerebral amyloid angiopathy, a group of heterogenous diseases presenting with aggregation of amyloid complexes and deposition predominantly in the central nervous system. HCCAA is dominantly inherited, caused by L68Q mutation in the cystatin C gene, leading to aggregation of the cystatin C protein. HCCAA is a very progressive and severe disease, with widespread cerebral and parenchymal cystatin C and collagen IV deposition within the central nervous system (CNS) but also in other organs in the body, for example, in the skin. Most L68Q carriers have clinical symptoms characterized by recurrent hemorrhages and dementia, between the age of 20-30 years. If the carriers survive the first hemorrhage, the frequency and severity of the hemorrhages tend to increase, resulting in death at average of 30 years with mean number of major hemorrhages ranging from 3.2 to 3.9 over a 5-year average life span. The pathogenesis of the disease in carriers is very similar in the CNS and in the skin based on autopsy studies, thus skin biopsies can be used to monitor the progression of the disease by quantifying the cystatin C immunoreactivity. The cystatin C deposition always colocalizes with collagen IV and fibroblasts in the skin are found to be the main cell type responsible for the deposition of both proteins. No therapy is available for this devastating disease.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13291"},"PeriodicalIF":5.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foxq1 activates CB2R with oleamide to alleviate POCD.","authors":"Xiaoying Wu, Yuming Wu, Fudong Tang, Yangyang Wang, Chenxi Li, Su Wu, Guangzhi Wang, Jiaqiang Zhang","doi":"10.1111/bpa.13289","DOIUrl":"https://doi.org/10.1111/bpa.13289","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a major concern, particularly among older adults. This study used social isolation (ISO) and multiomics analyses in aged mice to investigate potential mechanisms underlying POCD development. Aged mice were divided into two groups: ISO and paired housing (PH). Oleamide and the cannabinoid receptor type 2 (CB2R) antagonist AM630 were administered intraperitoneally, while Foxq1 adeno-associated viral (AAV) vector was injected directly into the hippocampus. Intramedullary tibial surgeries were subsequently performed to establish the POCD models. Behavioral tests comprising the Y-maze, open field test, and novel object recognition were conducted 2 days after surgery. Hippocampal and serum inflammatory cytokines were assessed. Following surgery, ISO mice demonstrated intensified cognitive impairments and escalated inflammatory markers. Integrative transcriptomic and metabolomic analysis revealed elevated oleamide concentrations in the hippocampus and serum of PH mice, with associative investigations indicating a close relationship between the Foxq1 gene and oleamide levels. While oleamide administration and Foxq1 gene overexpression substantially ameliorated postoperative cognitive performance and systemic inflammation in mice, CB2R antagonist AM630 impeded these enhancements. The Foxq1 gene and oleamide may be crucial in alleviating POCD. While potentially acting through CB2R-mediated pathways, these factors may modulate neuroinflammation and attenuate proinflammatory cytokine levels within the hippocampus, substantially improving cognitive performance postsurgery. This study lays the groundwork for future research into therapeutic approaches targeting the Foxq1-oleamide-CB2R axis, with the ultimate goal of preventing or mitigating POCD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13289"},"PeriodicalIF":5.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Ki-67 and mitoses in pituitary neuroendocrine tumours-Consistency counts.","authors":"Paul Benjamin Loughrey, Christine Greene, Kris D McCombe, Fatima Abdullahi Sidi, Stephen McQuaid, Stephen Cooke, Steven J Hunter, Brian Herron, Márta Korbonits, Stephanie G Craig, Jacqueline A James","doi":"10.1111/bpa.13285","DOIUrl":"https://doi.org/10.1111/bpa.13285","url":null,"abstract":"<p><p>Pituitary neuroendocrine tumour Ki-67 proliferation index varies according to the number of tumour cells assessed. Consistent Ki-67 scoring approaches and re-evaluation of the recommended Ki-67 3% cut-off are required to clarify controversies in pituitary neuroendocrine tumour Ki-67 proliferation index assessment.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13285"},"PeriodicalIF":5.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis.","authors":"Olivia M Rifai, Fergal M Waldron, Danah Sleibi, Judi O'Shaughnessy, Danielle J Leighton, Jenna M Gregory","doi":"10.1111/bpa.13287","DOIUrl":"https://doi.org/10.1111/bpa.13287","url":null,"abstract":"<p><p>Many genes have been linked to amyotrophic lateral sclerosis (ALS), including never in mitosis A (NIMA)-related kinase 1 (NEK1), a serine/threonine kinase that plays a key role in several cellular functions, such as DNA damage response and cell cycle regulation. Whole-exome sequencing studies have shown that NEK1 mutations are associated with an increased risk for ALS, where a significant enrichment of NEK1 loss-of-function (LOF) variants were found in individuals with ALS compared to controls. In particular, the p.Arg261His missense variant was associated with significantly increased disease susceptibility. This case series aims to understand the neuropathological phenotypes resulting from NEK1 mutations in ALS. We examined a cohort of three Scottish patients with a mutation in the NEK1 gene and evaluated the distribution and cellular expression of NEK1, as well as the abundance of phosphorylated TDP-43 (pTDP-43) aggregates, in the motor cortex compared to age- and sex-matched control tissue. We show pathological, cytoplasmic TDP-43 aggregates in all three NEK1-ALS cases. NEK1 protein staining revealed no immunoreactivity in two of the NEK1-ALS cases, indicating a LOF and corresponding to a reduction in NEK1 mRNA as detected by in situ hybridisation. However, the p.Arg261His missense mutation resulted in an increase in NEK1 mRNA molecules and abundant NEK1-positive cytoplasmic aggregates, with the same morphologic appearance, and within the same cells as co-occurring TDP-43 aggregates. Here we show the first neuropathological assessment of a series of ALS cases carrying mutations in the NEK1 gene. Specifically, we show that TDP-43 pathology is present in these cases and that potential NEK1 LOF can either be mediated through loss of NEK1 translation or through aggregation of NEK1 protein as in the case with p.Arg261His mutation, a potential novel pathological feature of NEK1-ALS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13287"},"PeriodicalIF":5.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper motor neuron-predominant motor neuron disease presenting as atypical parkinsonism: A clinicopathological study.","authors":"Aya Murakami, Shunsuke Koga, Shinsuke Fujioka, Adrianna E White, Kevin F Bieniek, Hiroaki Sekiya, Mariely DeJesus-Hernandez, NiCole A Finch, Marka van Blitterswijk, Masataka Nakamura, Yoshio Tsuboi, Melissa E Murray, Zbigniew K Wszolek, Dennis W Dickson","doi":"10.1111/bpa.13286","DOIUrl":"https://doi.org/10.1111/bpa.13286","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN-dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN-predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN-predominant MND. We reviewed 24 patients with UMN-predominant MND with TDP-43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically-confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically-confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN-predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN-predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN-predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN-predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13286"},"PeriodicalIF":5.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo","authors":"Nadja Straumann,&nbsp;Benjamin F. Combes,&nbsp;Xose Luis Dean Ben,&nbsp;Rebecca Sternke-Hoffmann,&nbsp;Juan A. Gerez,&nbsp;Ines Dias,&nbsp;Zhenyue Chen,&nbsp;Benjamin Watts,&nbsp;Iman Rostami,&nbsp;Kuangyu Shi,&nbsp;Axel Rominger,&nbsp;Christian R. Baumann,&nbsp;Jinghui Luo,&nbsp;Daniela Noain,&nbsp;Roger M. Nitsch,&nbsp;Nobuyuki Okamura,&nbsp;Daniel Razansky,&nbsp;Ruiqing Ni","doi":"10.1111/bpa.13288","DOIUrl":"10.1111/bpa.13288","url":null,"abstract":"<p>Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe³⁺ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562732","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}