Neuropathology最新文献

{"title":"Unprecedented Combination of Rare Degenerative Pathologies in an Octogenarian Ex-Football Player.","authors":"Shelley L Forrest, Nusrat Sadia, Mozhgan Khodadadi, Charles Tator, Robin Green, Maria Carmela Tartaglia, Gabor G Kovacs","doi":"10.1111/neup.70004","DOIUrl":"https://doi.org/10.1111/neup.70004","url":null,"abstract":"<p><p>A 79-year-old former professional football player presented with language deficits and cognitive changes. A year later, he had difficulty completing sentences, and 3 years after onset, was reduced to one-word answers. He developed severe apathy and agitation, and became more impulsive. He eventually became mute and had difficulty with walking and balance. The patient had mild repetitive head injury while playing football and three concussions. Magnetic resonance imaging revealed left > right frontotemporal atrophy. Duration of illness was 6 years. Neuropathology revealed an unexpected number and diversity of degenerative pathologies, including chronic traumatic encephalopathy (CTE, high level), high level Alzheimer's disease neuropathologic change (A3B3C3), limbic Lewy body disease, cerebral amyloid angiopathy (type 2), argyrophilic grain disease (Stage 2), and neuronal intranuclear hyaline inclusion body disease. In addition, there was selective and asymmetric involvement of the corticospinal tract with globular oligodendroglial tau pathology corresponding to globular glial tauopathy (Type II). The patchy and irregular accentuation of cortical tau pathology, particularly in the depths of sulci and accumulation around blood vessels, allows the diagnosis of CTE-neuropathologic change. This diagnosis correlated with the past medical history of multiple concussions. In addition, the patient had an unprecedented number and combination of additional degenerative pathologies, including those that are rare, and how they contributed to the clinical symptoms is difficult to interpret. Globular glial tauopathy Type II is a rare disorder that has been mostly reported in association with progressive supranuclear gaze palsy, and these observations support the notion that globular glial tauopathy Type II is an independent entity with isolated corticospinal tract involvement. These observations highlight that rare disorders can occur in the same individual and be overlooked, especially when there is more obvious pathology. It is essential for neuropathologists to consider an extensive array of neuropathological examinations when assessing patients with neurodegenerative disorders.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications for soluble iron accumulation, oxidative stress, and glial glutamate release in motor neuron death associated with sporadic amyotrophic lateral sclerosis.","authors":"Noriyuki Shibata, Ikuko Kataoka, Yukinori Okamura, Kumiko Murakami, Yoichiro Kato, Tomoko Yamamoto, Kenta Masui","doi":"10.1111/neup.13033","DOIUrl":"https://doi.org/10.1111/neup.13033","url":null,"abstract":"<p><p>Oxidative stress in sporadic amyotrophic lateral sclerosis (ALS) has been evidenced by accumulation of oxidatively modified products of nucleic acids, lipids, sugars, and proteins in the motor neuron system of brains and spinal cords obtained at autopsy from the patients. We recently demonstrated soluble iron accumulation in activated microglia of sporadic ALS spinal cords. This finding could indicate that iron-mediated Fenton reaction is most likely to be responsible for oxidative stress associated with this disease. The excitatory amino acid neurotoxicity hypothesis for sporadic ALS has been proposed based on increased glutamate and aspartate concentrations in cerebrospinal fluid from the patients. Initially, the increase in extracellular excitatory amino acid levels was considered to reflect excessive release from the axon terminal of upper motor neurons. However, it is a question of whether the damaged upper motor neurons continue releasing glutamate even in advanced stage of this disease. To address this issue, we hypothesized that glial cells might be a glutamate release source. Our immunohistochemical analysis on autopsied human spinal cords revealed that ferritin, hepcidin, ferroportin, aconitase 1, tumor necrosis factor-α (TNF-α), TNF-α-converting enzyme (TACE), and glutaminase-C (GAC) were expressed mainly in microglia and that cystine/glutamate antiporter (xCT) was expressed mainly in astrocytes. We next performed cell culture experiments. Cultured microglia treated with soluble iron over-released glutamate and TNF-α via aconitase 1 and TACE, respectively. Cultured microglia treated with TNF-α over-released glutamate via GAC. Cultured microglia treated with hepcidin, of which expression is known to be upregulated by TNF-α, showed downregulated expression of ferroportin. Cultured astrocytes treated with hydrogen peroxide over-released glutamate via xCT. These observations provide in vivo and in vitro evidence that microglia and astrocytes are glutamate suppliers in response to soluble iron overload and oxidative stress, respectively, in sporadic ALS.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Co-Localization of ITM2B With Alzheimer's Disease and Limbic-Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes.","authors":"Ryan K Shahidehpour, Peter T Nelson, Sukanya Srinivasan, Zhong Yu, Adam D Bachstetter","doi":"10.1111/neup.70003","DOIUrl":"https://doi.org/10.1111/neup.70003","url":null,"abstract":"<p><p>Mutations in the Integral membrane protein 2B (ITM2B) gene are linked to the development of familial British and Danish dementias, two relatively early-onset dementia disorders known also to be associated with Tau neurofibrillary tangles (NFTs). However, to date, the involvement of ITM2B in limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC) remains unclear. To address this question, we used brain samples from the University of Kentucky Alzheimer's Disease Research Center community-based autopsy cohort. We investigated the patterns and co-localizations of ITM2B immunohistochemistry in subiculum, CA1, CA2, CA3 and dentate gyrus of the hippocampus from brains with Alzheimer's disease neuropathologic changes (ADNC), LATE-NC, and comorbid ADNC+LATE-NC, as well as low-pathology controls (n = 4 per disease state). There was frequent co-localization between ITM2B protein and intracellular Tau pathology in ADNC; however, there was a far weaker rate of co-localization between ITM2B and TDP-43 pathology. There also was, as previously described, an association between ITM2B immunostaining and neuritic-appearing amyloid plaques. Additionally, co-localization of intracellular ITM2B pathology with Thioflavin-S in NFTs suggested a potential role for ITM2B in marking neurons undergoing transition from relatively healthy (early NFT-bearing cells) to more severely affected (later NFT-bearing) cellular disease states. This study indicates that ITM2B has a relatively specific pattern of involvement in Tau-related neurodegeneration and in neuritic amyloid plaques, while implying minimal, if any, role for ITM2B in the synergistic relationship between Tau and TDP-43 pathologies.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTX-2 Expression as a Diagnostic Marker for Choroid Plexus Tumors.","authors":"Ayça Erşen Danyeli, Zeynep Hüseyinoğlu, M Memet Özek","doi":"10.1111/neup.70001","DOIUrl":"https://doi.org/10.1111/neup.70001","url":null,"abstract":"<p><p>Choroid plexus tumors are neuroepithelium-derived tumors arising in the ventricles of the central nervous system. They are commonly seen in childhood and correspond to low rates in all central nervous system tumors. Due to their rareness and similar histomorphologic features to other tumors, their diagnosis might be challenging. Here, we used the OTX-2 antibody to evaluate the diagnostic role of OTX-2 expression in choroid plexus tumors. We performed a retrospective review of 34 patients operated for choroid plexus tumors in our center between 2011 and 2023. Additionally, as different tumor types are also arising in the ventricles, we selected five cases each of AT/RT, germ cell tumor, ependymoma, and metastatic adenocarcinoma from the pathology archive. Immunohistochemistry conditions were adjusted for each specific antibody based on the manufacturers' recommendations for concentrations and antigen retrieval/blocking. OTX-2, S-100, and transthyretin antibody staining was performed on sections from each case.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Neuropathologies Underly Hippocampal Subfield Atrophy in a Case With a Slowly Progressive Amnestic Syndrome: Challenging the Notion of Pure LATE-NC.","authors":"Hossam Youssef, Rodolfo G Gatto, Nha Trang Thu Pham, David Jones, Ronald C Petersen, Mary M Machulda, Jennifer L Whitwell, Keith A Josephs","doi":"10.1111/neup.70000","DOIUrl":"https://doi.org/10.1111/neup.70000","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia in the elderly, marked by abnormal protein buildup (beta-amyloid and tau) resulting in neuronal loss, especially in the medial temporal lobe and other limbic regions. The presence of transactive response DNA binding protein 43 (TDP-43) immunoreactive inclusions in medial temporal lobe regions has also been associated with neuroimaging changes in limbic regions. It has been proposed that hypometabolism in limbic regions on [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a slowly evolving amnestic syndrome may be a signature of the presence of TDP-43. In this context, we observed an 86-year-old Caucasian female with dementia characterized by a slowly evolving amnestic syndrome, along with focal medial temporal atrophy evident on MRI and hypometabolism in limbic regions on FDG-PET. The patient subsequently died and underwent an autopsy. We performed detailed neuroimaging and digital neuropathological analyses of the hippocampal subfields to better understand the relationship between clinico-imaging findings and histopathology. In addition to TDP-43, we identified three other pathological processes in the medial temporal lobe: sequestosome-1/p62, argyrophilic grain disease (AGD), and primary age-related tauopathy (PART). Hippocampal subfield volumes and rates of atrophy were no different from those of matched healthy controls, except for the atrophy rate in cornu ammonis 1 (CA1). Digital histopathology revealed the relative highest burden of pathology for p62, followed by TDP-43, AGD, and PART in CA1. Multiple pathological processes appear to have contributed to the hippocampal atrophy and hypometabolism in our patient with a slowly progressive amnestic syndrome.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vanishing Contrast Enhancement of a Diffuse Midline Glioma.","authors":"Charles Champeaux Depond, Philippe Metellus, Emmanuel Gross, Romain Appay","doi":"10.1111/neup.70002","DOIUrl":"https://doi.org/10.1111/neup.70002","url":null,"abstract":"<p><p>Diffuse midline glioma, is a highly aggressive deep-seated glioma whose diagnosis must be confirmed through histopathological analysis of stereotactic biopsies. Hemorrhagic complications after intracranial biopsies may occur, potentially leading to severe neurological sequelae or significantly altering the outcome. A 55-year old male with no significant medical history presented to the local emergency department with 4 days of diplopia. A magnetic resonance imaging (MRI) confirmed the presence of tumor whose characteristics were highly suggestive of a high-grade infiltrating causing blocked hydrocephalus. As no safe resection was achievable, a third ventriculostomy followed by an endoscopic biopsy of the tumor was performed. Unfortunately, the procedure was complicated by an massive intraventricular bleeding of the tumor and, the tiny tumor specimens collected were not contributive. Fortunately, the patient survived and, his clinical state slowly improved. Follow up MRIs depicted a progressive regression of the tumor. As such a wait and see policy was preferred over a chemoradiotherapy. Ultimately, the gadolinium enhancement totally vanished. Unfortunately, 27 months after the initial presentation, he presented with a quick neurological worsening with severe hemiparesis and seizures for which cerebral imaging showed a malignant-looking deep-situated unresectable brain tumor. A second biopsy was performed without any specific complication. The histopathological examination of the tumor revealed a high-grade glial tumor characterized by hypercellularity, marked atypia, mitosis, microvascular proliferation, and areas of necrosis with positive H3 p.K28M nuclear staining in combination with the loss of nuclear H3 p.K28me3. He was referred for best supportive care and, died 29.6 months after the initial presentation. To our knowledge, this is the first report of the gadolinium enhancement of a diffuse midline glioma H3 K27-altered.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some comments on the morphometry of choroid plexus in neurodegenerative diseases.","authors":"Jean-Marie Serot, Marie Christine Bene, Gilbert Charles Faure","doi":"10.1111/neup.13032","DOIUrl":"https://doi.org/10.1111/neup.13032","url":null,"abstract":"","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging minds: Participant perspectives on postmortem brain research and engagement.","authors":"Yusuke Inoue, Maki Obata, Maho Morishima, Shigeo Murayama, Yuko Saito","doi":"10.1111/neup.13030","DOIUrl":"https://doi.org/10.1111/neup.13030","url":null,"abstract":"<p><p>Postmortem research participation remains underrepresented in research ethics discussions. Herein, we examined the associated perspectives of individuals preregistered with the Brain Bank for Aging Research at the Tokyo Metropolitan Institute of Gerontology. We conducted a postal survey targeting 88 preregistrants, yielding 52 responses (response rate: 59.1%, average respondent age: 79.5 years, range: 49-97). The questionnaire gathered information on the reasons for agreeing to participate, helpful information provided during the explanation, and expectations regarding future information. The stated reasons for participating included a desire to contribute to science, gratitude for medical care received, memories of relatives' past donations, and inspiration from staff enthusiasm and materials. Beneficial information was given in brochures, coordinator explanations, and lectures; however, guidance for family members regarding postmortem procedures and updates on recent activities and research outcomes were highlighted as areas requiring future improvement. Willingness to participate in brain banks was influenced by altruistic factors, personal medical experiences, and the influence of statements from close contacts. Registrants maintained their interest after registration and prepare for future arrangements. Family cooperation was identified as a critical factor influencing the fulfillment of participant intentions, emphasizing the need for accessible and low-burden family guidance. Registrants generally seek information to help family members and associates avoid difficulties related to their participation. Brain banks should continue conducting such surveys for registrants and reflect the findings in their information dissemination and educational programs. This approach will help improve the understanding and support for brain bank participation, ultimately contributing to the advancement of medical research and ethics in postmortem studies.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autopsy case of coexisting spinal and bulbar muscular atrophy and multiple system atrophy.","authors":"Motoki Miura, Hiroshi Shintaku, Yoshiyuki Numasawa, Kokoro Ozaki, Tadashi Kanouchi, Kinya Ishikawa, Takanori Yokota","doi":"10.1111/neup.13031","DOIUrl":"https://doi.org/10.1111/neup.13031","url":null,"abstract":"<p><p>Here, we report an autopsy case of concurrent spinal and bulbar muscular atrophy (SBMA) and multiple system atrophy (MSA). A 55-year-old man presented with weakness, atrophy, and fasciculation of the tongue and the proximal parts of all limbs. The patient gradually developed severe orthostatic hypotension, urinary retention, and cerebellar ataxia; however, no parkinsonism was observed. The patient succumbed to sudden death during sleep. The autopsy revealed widespread and abundant α-synuclein-positive glial cytoplasmic inclusions in the central nervous system, indicative of MSA. Neuronal loss was also observed in the substantia nigra and locus coeruleus. Consequently, the patient was diagnosed with MSA. Additionally, immunostaining for the monoclonal 1C2 antibody revealed positive neurons in the medulla oblongata and spinal cord, supporting the additional diagnosis of SBMA. Genetic analysis revealed an expansion of 41 CAG repeats in the androgen receptor (AR) gene (normal range: 12-38), confirming the diagnosis of SBMA. Altogether, concurrent SBMA and MSA were diagnosed based on the autopsy findings, making this the first reported case of such coexistence in the Japanese and English literature.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of late-life blood pressure with CERAD, Braak, and Thal: Findings from the National Alzheimer's coordinating center neuropathology dataset.","authors":"Mo-Kyung Sin, N Maritza Dowling, Jeffrey M Roseman, Ali Ahmed, Edward Zamrini","doi":"10.1111/neup.13029","DOIUrl":"10.1111/neup.13029","url":null,"abstract":"<p><p>Mid-life high blood pressure (BP) is a risk factor for Alzheimer's disease (AD). CERAD amyloid β (Aβ) plaques, Braak tau neurofibrillary tangles, and Thal Aβ plaque location are major scoring systems for quantifying neuropathological features of AD. We examined the association of late-life systolic BP (SBP) with CERAD, Braak, and Thal in the National Alzheimer's Coordinating Center (NACC) Neuropathology Dataset. Of 1978 participants with data on CERAD, 762 had scores 0-1 (none to sparse) and 1216 had 2-3 (moderate to frequent). Of 1947 with data on Braak, 411 had stages 0-II (normal to mild) and 1536 had III-VI (moderately to very severe). Of 2132 with data on Thal, 438 had phases 0-I, 428 II-III, and 1266 IV-V. Using the mean of the last four SBP before death, SBP was categorized into <120 (references), 120-139, and ≥140 mmHg. Age-sex-adjusted ORs (95% CIs) associated with SBP ≥140 mmHg for CERAD 2-3 and Braak III-VI were 1.37 (1.03, 1.83, P = 0.03) and 1.26 (0.89, 1.78, P = 0.20), respectively. Similar association was observed for Thal II-III and IV-V. These associations essentially remained unchanged after additional adjustment for APOE and Lewy Body pathology. These findings suggest that higher late-life SBP is associated with markers of presence and severity of neuropathological features of AD. Further studies with larger sample sizes are necessary to confirm the findings.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}