Neuropathology and Applied Neurobiology最新文献

{"title":"Computational Analysis of SOD1-G93A Mouse Muscle Biomarkers for Comprehensive Assessment of ALS Progression.","authors":"Pedro Gómez-Gálvez, Victoria Navarro, Ana M Castro, Carmen Paradas, Luis M Escudero","doi":"10.1111/nan.70014","DOIUrl":"https://doi.org/10.1111/nan.70014","url":null,"abstract":"<p><strong>Aims: </strong>To identify potential image biomarkers of neuromuscular disease by analysing morphological and network-derived features in skeletal muscle biopsies from a murine model of amyotrophic lateral sclerosis (ALS), the SOD1^G93A mouse and wild-type (WT) controls at distinct stages of disease progression.</p><p><strong>Methods: </strong>Using the NDICIA computational framework, we quantitatively evaluated histological differences between skeletal muscle biopsies from SOD1^G93A and WT mice. The process involved the selection of a subset of features revealing these differences. A subset of discriminative features was selected to characterise these differences, and their temporal dynamics were assessed across disease stages.</p><p><strong>Results: </strong>Our findings demonstrate that muscle pathology in the mutant model evolves from early alterations in muscle fibre arrangement, detectable at the presymptomatic stage through graph theory features, to the subsequent development of the typical morphological pattern of neurogenic atrophy at more advanced disease stages.</p><p><strong>Conclusions: </strong>Our assay identifies a neurogenic signature in mutant muscle biopsies, even when the disease is phenotypically imperceptible.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 2","pages":"e70014"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753640","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":"Pathological Characterisation of Posterior Cortical Atrophy in Comparison With Amnestic Alzheimer's Disease.","authors":"Z Abdi, K X Yong, J M Schott, A Gatt, T Revesz, S J Crutch, T Lashley","doi":"10.1111/nan.70007","DOIUrl":"10.1111/nan.70007","url":null,"abstract":"<p><strong>Aims: </strong>Posterior cortical atrophy (PCA) is a predominantly young-onset neurodegenerative syndrome, typically caused by Alzheimer's disease (PCA-AD). PCA-AD presents with visual and spatial dysfunction attributed to occipito-parietal or 'posterior' brain regions rather than memory difficulties characteristic of typical amnestic-led Alzheimer's disease (a-AD) attributed to medial temporal regions. Imaging and neuropathological studies suggest that PCA-AD is associated with a more posterior distribution of tau neurofibrillary tangles (NFTs), whereas β-amyloid pathology (Aβ) is diffusely deposited throughout the cortex. This study characterised the neuropathological substrates of PCA-AD in comparison with a-AD, to further understanding of the biological basis of phenotypical heterogeneity in AD.</p><p><strong>Methods: </strong>Immunohistochemistry for Aβ; tau; the microglial markers CD68, CR3-43 and Iba1; α-synuclein; and TDP-43 was carried out on 26 PCA-AD and 27 age and gender-matched a-AD cases at the Queen Square Brain Bank. Aβ, tau and the three microglial markers were quantified in the superior frontal, superior temporal, superior parietal and occipital (primary visual cortex) cortices, with α-synuclein and TDP-43 assessed using formal staging criteria. In addition, microglial circularity, a morphological indicator of microglial activation state, was calculated.</p><p><strong>Results: </strong>There was a higher load of Aβ and tau in the parietal region of PCA-AD compared to a-AD. In the PCA-AD compared to the a-AD group, there were significant increases in tau load in parietal and frontal relative to temporal regions. There was no difference in cerebral amyloid angiopathy (CAA) severity between PCA-AD and a-AD. There was a significantly lower temporal CD68 load in a-AD compared with PCA-AD. In a-AD, CD68 load was lowest and tau load highest in the temporal relative to all other regions.</p><p><strong>Conclusions: </strong>This study demonstrates differences in the distribution of Aβ and tau and variations in regional neuroinflammatory response in PCA-AD and a-AD. These findings extend our understanding of the biological substrates underpinning PCA-AD and highlight the potential for exploring phenotypic variants to understand selective vulnerability in neurodegenerative diseases.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 2","pages":"e70007"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772940","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":"Intramuscular Nerve Bundles Reflect TDP-43 Pathology in the Medulla and Spinal Cord of ALS Patients.","authors":"Takashi Kurashige, Tomomi Murao, Yuhei Kanaya, Yoriko Dodo, Tomohito Sugiura, Kazuya Kuraoka, Tomohiko Ohshita","doi":"10.1111/nan.70016","DOIUrl":"10.1111/nan.70016","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 2","pages":"e70016"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796021","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":"Comparative Clinical and Imaging-Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification.","authors":"Michaela-Kristina Keck, Anna Tietze, Brigitte Bison, Shivaram Avula, Julien Engelhardt, Cécile Faure-Conter, Tanguy Fenouil, Dominique Figarella-Branger, Einar Goebell, Johannes Gojo, Christine Haberler, Juhana Hakumäki, James T Hayden, Laura S Korhonen, Ewa Koscielniak, Christof M Kramm, Mariëtte E G Kranendonk, Maarten Lequin, Louise E Ludlow, David Meyronet, Per Nyman, Ingrid Øra, Thomas Perwein, Jouni Pesola, Tuomas Rauramaa, Roel Reddingius, David Samuel, Antoinette Y N Schouten-van Meeteren, Alexandra Sexton-Oates, Alexandre Vasiljevic, Thekla von Kalle, Annika K Wefers, Pieter Wesseling, Josef Zamecnik, Michal Zapotocky, Katja von Hoff, David T W Jones","doi":"10.1111/nan.70015","DOIUrl":"10.1111/nan.70015","url":null,"abstract":"<p><strong>Aims: </strong>Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens.</p><p><strong>Methods: </strong>We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified).</p><p><strong>Results: </strong>Patients with PLAGL1-amplified tumours (ET, PLAGL1) had fewer relapses (3/9), while PLAGL2-amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8/9) and to distant, leptomeningeal and intraventricular relapses. Progression-free survival differed significantly between the subtypes (log-rank test, p = 0.0055). Postoperative treatment included chemotherapy (n = 17, various protocols), alone (n = 8) or combined with radiotherapy (n = 9). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high-dose chemotherapy with (n = 1-low-dose CSI and boost) or without (n = 2) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (n = 4-local radiotherapy n = 3; CSI and boost n = 1) or without (n = 2) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8 years.</p><p><strong>Conclusions: </strong>Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high-dose chemotherapy or craniospinal irradiation.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 2","pages":"e70015"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803528","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":"Novel Aspects of Hereditary Spastic Paraplegia: A Clinicopathologic and Biochemical Study of a Patient With a Heterozygous GCH1 Variant.","authors":"Shoko Hongo, Tetsuhiko Ikeda, Mari Tada, Rina Aida, Tetsuo Ozawa, Norikazu Hara, Akinori Miyashita, Takashi Nakajima, Osamu Onodera, Takeshi Ikeuchi, Hiroshi Ichinose, Akiyoshi Kakita","doi":"10.1111/nan.70006","DOIUrl":"https://doi.org/10.1111/nan.70006","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 1","pages":"e70006"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493045","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":"Neuroinvasion via Peripheral Nerves in Epidemic Viral Encephalitis Caused by Enterovirus, Orthoflavivirus and SARS-Coronavirus.","authors":"Yuan Teng Hooi, Tzeh Long Fu, Soon Hao Tan, Kien Chai Ong, Chee Yang Tan, Kum Thong Wong","doi":"10.1111/nan.70005","DOIUrl":"https://doi.org/10.1111/nan.70005","url":null,"abstract":"<p><p>Pathogens invade the central nervous system (CNS) and cause infections either through the haematogenous route or via peripheral nerves. Neuroinvasion via peripheral nerves, involving spinal or cranial somatic nerves, is well-established for certain viral encephalitides such as rabies, herpes simplex encephalitis, and poliomyelitis. Advances in understanding emerging and re-emerging viruses that cause epidemic CNS infections have highlighted the growing importance of peripheral nerve pathways in viral neuroinvasion. This review focuses on epidemic viral encephalitides caused by three groups of RNA viruses, viz., enteroviruses (enterovirus A71 and enterovirus D68), orthoflaviviruses (West Nile virus and Japanese encephalitis virus), and severe acute respiratory syndrome coronaviruses (mainly severe acute respiratory coronavirus-2). We examine evidence supporting the hypothesis that peripheral nerve viral transmission may play an increasingly significant if not more critical role than the haematogenous route in neuroinvasion.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 1","pages":"e70005"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483726","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 Homozygous ATP2A2 Variant Alters Sarcoendoplasmic Reticulum Ca²⁺-ATPase 2 Function in Skeletal Muscle and Causes a Novel Vacuolar Myopathy.","authors":"Laura Llansó, Gianina Ravenscroft, Cristina Aceituno, Antonio Gutiérrez, Jevin Parmar, Pia Gallano, Marta Caballero-Ávila, Álvaro Carbayo, Ana Vesperinas, Roger Collet, Rosa Blanco, Nigel Laing, Leif Hove-Madsen, Eduard Gallardo, Montse Olivé","doi":"10.1111/nan.70000","DOIUrl":"10.1111/nan.70000","url":null,"abstract":"<p><strong>Aims: </strong>Sarcoendoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), encoded by ATP2A2, is a key protein involved in intracellular Ca²⁺ homeostasis. The SERCA2a isoform is predominantly expressed in cardiomyocytes and type I myofibres. Variants in this gene are related to Darier disease, an autosomal dominant dermatologic disorder, but have never been linked to myopathy. We describe four patients suffering from a novel myopathy caused by a homozygous missense variant in ATP2A2.</p><p><strong>Methods: </strong>We studied a family with four individuals suffering from an adult-onset skeletal myopathy. We evaluated the clinicopathological phenotype, muscle imaging, and genetic workup including whole genome sequencing and segregation analysis. SERCA2 expression in skeletal muscle was assessed. Functional studies to evaluate Ca²⁺ handling in patient myotubes in response to electrical stimulation or caffeine exposure were performed.</p><p><strong>Results: </strong>Four sisters developed slowly progressive proximal weakness in adulthood. Biopsy findings showed small vacuoles restricted to type I myofibres. Ultrastructural analysis showed sarcotubular dilation and autophagic vacuoles. Genome sequencing revealed a homozygous variant in ATP2A2 (c.1117G > A, p.(Glu373Lys)) which segregated with the disease. Immunohistochemistry suggested that there was SERCA2 mislocalisation in patient myofibres. Western blotting did not show changes in the amount of protein. In vitro functional studies revealed delayed sarcoendoplasmic reticulum Ca²⁺ reuptake in patient myotubes, consistent with an altered pumping capacity of SERCA2 after cell stimulation.</p><p><strong>Conclusions: </strong>We report a novel adult-onset vacuolar myopathy caused by a homozygous variant in ATP2A2. Biopsy findings and functional studies demonstrating an impaired function of SERCA2 and consequent Ca²⁺ dysregulation in slow-twitch skeletal myofibres highly support the pathogenicity of the variant.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 1","pages":"e70000"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008819","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":"Neuromuscular Junction Damage in the Calf Muscles of Patients With Advanced Peripheral Artery Disease.","authors":"Huiyin Tu, Ali H Hakim, Julian K Kim, Zhen Zhu, Yuqian Tian, Iraklis I Pipinos, Yu-Long Li","doi":"10.1111/nan.70008","DOIUrl":"10.1111/nan.70008","url":null,"abstract":"<p><strong>Aims: </strong>Peripheral artery disease (PAD) reduces blood flow to the legs and causes severe muscle and leg dysfunction for PAD patients. Skeletal muscle contractile function is dependent on the health of the muscle itself and that of the neuromuscular junction (NMJ) on the muscle membrane.</p><p><strong>Methods: </strong>To determine whether the NMJ, including the motor nerve terminals and nicotinic acetylcholine receptors (nAChR), is damaged in PAD, gastrocnemius muscles were collected from 3 controls and 13 PAD patients to capture images from 331 control NMJs and 512 PAD NMJs.</p><p><strong>Results: </strong>For the motor nerve terminals, there were more denervated nAChR clusters and fewer nerve terminal occupancies in NMJs in PAD patients, compared with controls. For the nAChR clusters in the NMJs, the area per nAChR cluster was 369.3 ± 6.7 versus 225.2 ± 5.3 μm², the area per fragment was 195.9 ± 9.2 versus 107.1 ± 3.1 μm², the number of fragments per nAChR cluster was 2.3 ± 0.1 versus 3.2 ± 0.1, the nAChR cluster area per endplate area was 75.7 ± 1.6 versus 55.7 ± 1.1%, total distance of fragments per nAChR cluster was 4.6 ± 0.4 versus 8.8 ± 0.8 μm, and the fragmented nAChR clusters were 7.6% versus 21.6% of total nAChR clusters in controls versus PAD patients, respectively (p < 0.05 in all parameters).</p><p><strong>Conclusions: </strong>Our data demonstrate deterioration of the motor nerve terminals and nAChR clusters, which may compromise neuromuscular transmission, and contribute to the severe leg dysfunction observed in patients with PAD.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 1","pages":"e70008"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483727","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":"Proceedings of the 126^th Meeting of the British Neuropathological Society 29-31 January 2025, London, UK.","authors":"","doi":"10.1111/nan.70004","DOIUrl":"https://doi.org/10.1111/nan.70004","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 Suppl 1 ","pages":"e70004"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059606","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":"Author Index.","authors":"","doi":"10.1111/nan.70002","DOIUrl":"https://doi.org/10.1111/nan.70002","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 Suppl 1 ","pages":"e70002"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059598","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}