Neuropathology and Applied Neurobiology最新文献

{"title":"Myopathology and Immune Profile of Granulomatous Myositis in Sarcoid Myopathy.","authors":"Nikolas Ruffer, Iago Pinal-Fernandez, Felix Kleefeld, Marie-Therese Holzer, Hans-Hilmar Goebel, Anne Schänzer, Maria Casal-Dominguez, Ina Kötter, Norman Görl, Florian Masuhr, Rieke Alten, Eckart Braasch, Albert Grüger, Jörg Müller, Thomas Lempert, Andreas Krause, Tobias B Huber, Teerin Liewluck, Andrew L Mammen, Werner Stenzel, Corinna Preusse, Udo Schneider, Martin Krusche","doi":"10.1111/nan.70040","DOIUrl":"10.1111/nan.70040","url":null,"abstract":"<p><strong>Aims: </strong>Sarcoid myopathy (SaM) is characterised by granulomatous myositis (GM) and can overlap with inclusion body myositis (IBM), a late-onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. As GM can occur in different clinical contexts, we aimed to examine the histomorphologic features and gene expression profiles in cases of definite SaM that may inform diagnostic and therapeutic considerations.</p><p><strong>Methods: </strong>We performed a multidimensional characterisation of muscle biopsy specimens from patients with 'pure SaM' (n=17), SaM with concomitant IBM (SaM-IBM) (n=2), including histopathologic and ultrastructural analysis in addition to quantitative real-time polymerase chain reaction. Additionally, bulk RNA sequencing was performed on 38 muscle biopsy specimens from patients with SaM (including SaM-IBM) (n=30) and NGI (n=8).</p><p><strong>Results: </strong>Histopathological analysis revealed a pattern of endomysial and perimysial granulomatous inflammation frequently extending to the fascia, endomysial fibrosis, muscle fibre atrophy, variation in muscle fibre size and capillary thickening. Findings from immunohistochemical studies established Chitinase 1 as a pure giant cell marker in SaM. On a subcellular level, 'pure SaM' was characterised by focal accumulation of large swollen mitochondria with rare cristae but an absence of irregular cristae. Transcriptomic analysis of patients with SaM confirmed markedly elevated expression of both type 1 and type 2 human leukocyte antigen molecules. Macrophage activity markers were highly elevated. Consistent with histologic findings, CHIT1 was specifically overexpressed in SaM samples but not in 'pure IBM' muscle biopsy specimens.</p><p><strong>Conclusions: </strong>SaM is characterised by a stereotypical appearance at the histopathologic level and disease-specific immune dysregulation that involves macrophage function and maturation. SaM-IBM represents a noteworthy overlap syndrome that shares multiple dysregulated immune pathways with 'pure SaM'.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70040"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030128","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":"A Specific Methylation Class Identifies BAP1-Deficient Meningiomas, Including Meningeal Tumours With Poorly Differentiated Nonrhabdoid Histology.","authors":"Philippe Drabent, Mehdi Touat, Patrick R Benusiglio, Philipp Euskirchen, Florence Coulet, Badreddine Mohand Oumoussa, Arnaud de la Fouchardière, Vincent Thomas de Montpreville, Julian Jacob, Daniele Bernardeschi, Pierre Laurent-Puig, Marc Sanson, Michel Kalamarides, Franck Bielle","doi":"10.1111/nan.70042","DOIUrl":"10.1111/nan.70042","url":null,"abstract":"<p><p>BAP1-deficient meningiomas have a preferential infratentorial or spinal localization and may present with an undifferentiated histology of small or epithelioid cells rather than the meningothelial, rhabdoid or papillary variants. Frequent expression of cytokeratins may be misleading for a metastatic carcinoma but loss of BAP1 immunostaining in tumor cells and a specific methylation class enable the diagnosis. The clinical impact of the histomolecular diagnosis of BAP1-deficient meningioma is the high risk of relapse and a possible underlying BAP1 tumour predisposition syndrome.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70042"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192189","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":"Role of Astrocytic and Microglial Phenotype in the Biology of Hippocampal Sclerosis.","authors":"Aditi Goyal, Shilpa Rao, Amit Kumar Saha, Harsha Sugur, Roshni Poulose, Omkar Shirke, Nivedha Mohanraj, Bhupesh Mehta, Mariamma Philip, A Arivazhagan, Jitender Saini, L G Vishwanathan, Ajay Asranna, K Raghavendra, R C Mundlamuri, Nishanth Sadashiva, R D Bharath, K Karthik, M Sandhya, Malla Bhaskara Rao, Sanjib Sinha, Anita Mahadevan","doi":"10.1111/nan.70044","DOIUrl":"10.1111/nan.70044","url":null,"abstract":"<p><strong>Aims: </strong>Astrocytic and microglial phenotypes (A1/A2 and M1/M2, respectively) with neuro-inflammatory and neuroprotective roles are key players in the pathogenesis of several neurological diseases. However, their role in epilepsy is underexplored. We investigated astrocytic and microglial phenotypes in the pathogenesis of epileptogenesis in hippocampal sclerosis (HS), causing drug-resistant temporal lobe epilepsy.</p><p><strong>Methods: </strong>Astrocytic and microglial phenotypes were assessed in 10 histologically confirmed cases of surgically resected HS and four age-matched post-mortem controls by immunohistochemistry, using C3 and GBP2 (A1-astrocyte), pSTAT3 (A2-astrocyte), CD14 (M1-microglia) and CD163 and CD206 (M2-microglia), as well as Caspase 3 (apoptosis) and phosphorylated-tau and phosphorylated-neurofilament (pNF) (neuronal degeneration). These were semiquantitatively assessed for their expression in sclerotic hippocampus. Validation was carried out by immunoblotting and quantitative real-time polymerase chain reaction (RT-PCR). Results of the glial phenotypes were correlated with clinical parameters.</p><p><strong>Results: </strong>Compared to the control group, a significant increase in pSTAT3+ A2-astrocytes was detected (range: 26.7-230.5 cells/mm²) compared to a mild increase in GBP2+ A1-astrocytes (0.4-11.4 cells/mm²). pSTAT3 expression was localised to subpial astrocytes and vascular endothelial cells, aligning with subpial gliosis and vascular sclerosis observed in HS. The findings were confirmed by RT-PCR, reflecting a predominantly reparative and neuroprotective A2 response to chronic seizure activity in HS. Among microglial phenotypes, perivascular staining with CD14+ M1 (6-23.7 vessels/mm²) and CD163+ M2-microglia (7.4-16 vessels/mm²) was significantly higher in hippocampal subfields showing neuronal loss and gliosis. Predominant inflammatory M1-microglia, along with an increase in M2-microglia, indicate an ongoing reparative response to chronic epilepsy. Surviving neurons in sclerotic Ammon's horn (AH) were labelled by pNF, indicating dysmorphic change. Several astrocytes and oligodendroglia in hippocampal AH and temporal white matter were labelled by caspase 3, probably promoting gliosis rather than apoptosis.</p><p><strong>Conclusions: </strong>This is the first study providing a comprehensive assessment of astrocytic and microglial phenotypes in HS. These identified phenotypes can be targeted in multiple stages, offering potential modulation of epileptogenesis and contributing to the treatment of epilepsy, especially in cases marked by drug resistance.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70044"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252247","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":"Palmitoyl-Protein Thioesterase 1 (PPT1) Protein, Linked to Neuronal Ceroid Lipofuscinosis 1, Is a Major Constituent of Ageing-Related Human Neuronal Lipofuscin.","authors":"Max Anstötz, Sarah Tschirner, Caroline May, Steffen Kösters, Christine Martin, Svenja Caspers, Eleonora Aronica, Hans Jürgen Bidmon, Katrin Marcus, Carsten Korth","doi":"10.1111/nan.70043","DOIUrl":"10.1111/nan.70043","url":null,"abstract":"<p><p>Proteomics of laser-dissected lipofuscin from aged, healthy brains reveals Palmitoyl-Protein Thioesterase 1 (PPT1) and other CLN proteins as constituents. PPT1 is increasingly sequestered to lipofuscin during ageing. Protein sequestering into lipofuscin may contribute to physiological neuronal ageing.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70043"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131625","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":"Intrahippocampally Injected Human Recombinant Clusterin Reduces Amyloid-β Aggregate Size in Cerebral Arteriole Walls of Clusterin Knockout Mice.","authors":"Alexandru Laslo, Tudor-Gabriel Boghițoiu, Laura Chinezu, Doina Manu, Adrian Dumitru Ivanescu, Bogdan Andrei Cordoș, Mark R Wilson, Claudia Banescu, John D Fryer, Ajay Verma, Jennifer M Dewing, Roxana-Octavia Carare","doi":"10.1111/nan.70037","DOIUrl":"10.1111/nan.70037","url":null,"abstract":"<p><strong>Aims: </strong>The clusterin (CLU) gene is genetically associated with Alzheimer's disease (AD), and CLU levels have been shown to positively correlate with regional Aβ deposition in the brain, including in arteries from cerebral amyloid angiopathy (CAA) patients. CLU has also been shown to alter the aggregation, toxicity and blood-brain barrier transport of amyloid beta (Aβ) and has therefore been suggested to play a key role in regulating the balance between Aβ deposition and clearance in both the brain and cerebral blood vessels. However, it remains unclear whether the role of clusterin in relation to Aβ deposition is protective or pathogenic. The aim of this study was to determine how the presence of clusterin influences the pattern of Aβ deposition in hippocampal cerebral vessels.</p><p><strong>Methods: </strong>Intrahippocampal injections of fluorescent human recombinant Aβ alone or in combination with human recombinant CLU were carried out in Clu knockout mice. Aβ deposition and aggregate size in arterioles and capillaries were assessed by confocal microscopy.</p><p><strong>Results: </strong>The presence of CLU significantly reduced the size of Aβ deposits in the walls of cerebral arterioles but not in the tissue outside arterioles. There was no significant difference in overall Aβ deposition within cerebral arterioles and capillaries of mice injected with Aβ + CLU versus Aβ alone.</p><p><strong>Conclusions: </strong>Our findings confirm that CLU directly impacts cerebral vascular Aβ aggregation, the implications of which are particularly relevant to CAA, which is a major cause of cerebral haemorrhage and cognitive decline, particularly in individuals with AD.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70037"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015884","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":"Use of DNA Methylation Profiling as a Molecular Classification Tool for Paediatric Central Nervous System Tumours: A Middle-Income Country Population-Based Study.","authors":"Mayara F Euzébio, Felipe L T Silva, Iva L Hoffmann, Juliana S Ruas, Larissa Akemi Kido, Dieila G de Lima, Luciano Queiroz, Izilda A Cardinalli, Ana Luiza Seidinger, Suelen Nascimento, Helder Tedeschi, Renato D Puga, Priscila Pini Zenatti Sales, Patricia Y Jotta, Mariana Maschietto","doi":"10.1111/nan.70041","DOIUrl":"10.1111/nan.70041","url":null,"abstract":"<p><p>Paediatric central nervous system (CNS) tumours are the second most common childhood malignancy and the leading cause of cancer-related mortality in this age group. Histopathological diagnosis can be challenging, particularly for rare or ambiguous tumours, and may result in misclassification. To evaluate the utility of DNA methylation profiling in a middle-income country, we performed the Infinium MethylationEPIC BeadChip (Illumina) on tumours from 182 paediatric patients treated at a reference centre for paediatric oncology in Campinas, state of São Paulo, Brazil. Data were analysed using the DKFZ/Heidelberg CNS tumour classifier (v12.8). After excluding control tissue, 163 samples (89.6%) were suitable for classification; 135 (74.2%) achieved a calibrated score ≥ 0.9 and were assigned to a methylation class family. Methylation profiling resulted in a tumour subtype for 88 cases (65.7%) and changed the diagnosis in 28 cases (20.9%), identifying several rare tumour subtypes that were identified solely through methylation analysis, confirming the value of this method in improving diagnostic accuracy. This study highlights the utility of DNA methylation profiling for paediatric CNS tumours in a resource-limited setting and provides a cohort from an underrepresented middle-income population to international molecular databases.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 5","pages":"e70041"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207076","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":"Protein Coaggregation in Caribbean Atypical Parkinsonism: The Contribution of Annonacin.","authors":"Florencia González-Lizárraga, Susana Boluda, José Ruiz Hidalgo, Cesar L Avila, Camille Dos Santos, Benjamin Socias, Luciana Medina, Hugo Chaumont, David Akbar, Emmanuel Roze, Rosana Chehin, Rita Raisman-Vozari, Patrick Pierre Michel, Annie Lannuzel","doi":"10.1111/nan.70026","DOIUrl":"10.1111/nan.70026","url":null,"abstract":"<p><strong>Aims: </strong>There is an unexpectedly high proportion of atypical forms of degenerative parkinsonism in the French Caribbean islands. Residents of these islands are thought to be susceptible to Caribbean atypical parkinsonism (CAP) owing to their consumption of Annonaceae plant products containing the mitochondrial toxin annonacin. Here, we aimed to better correlate the clinical diagnosis of CAP with the misfolded protein pathology observed in affected individuals and to further investigate how annonacin could contribute to CAP pathogenesis.</p><p><strong>Methods: </strong>We conducted postmortem histopathological analysis of brain samples from eight patients; more specifically, we assessed the distribution and burden of α-synuclein (αS) and tau pathologies. Additionally, we studied how annonacin influences αS and tau aggregation using biophysical assays, with the corresponding recombinant human proteins serving as substrates.</p><p><strong>Results: </strong>CAP was associated with heterogeneous clinical and histopathological features. Tau/αS copathology with a predominance of either αS or tau aggregates was observed in the majority (5/8) of patients. Tau and αS aggregates were sometimes colocalised in the same brain regions or cells. In biophysical assays, we showed that annonacin leads to an increase in αS aggregation and the formation of αS fibrils that could cross-seed tau aggregation.</p><p><strong>Conclusions: </strong>Annonacin may contribute to degenerative CAP by modulating the production of tau and αS pathogenic protein assemblies.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 4","pages":"e70026"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699117","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":"Clinicopathological Characteristics and Immune Microenvironment of Posterior Pituitary Tumours.","authors":"Yu-Jie Li, Wei Wang, An-Li Zhang, Heng Li, Hai-Bo Wu","doi":"10.1111/nan.70029","DOIUrl":"10.1111/nan.70029","url":null,"abstract":"<p><strong>Aims: </strong>Posterior pituitary tumours (PPTs) represent a distinct group of low-grade neoplasms characterised by unique pathological features and immunohistochemical phenotypes. However, their precise immunological environment remains poorly understood, posing challenges to a deeper understanding of their biological behaviour and potential treatment implications. This study aimed to characterise the clinicopathological features and immune landscape of PPTs, focusing on the infiltration patterns of T cells and macrophages.</p><p><strong>Methods: </strong>Sixteen PPTs were retrospectively analysed, including 10 pituicytomas (PC) and six spindle cell oncocytomas (SCO), using clinicopathological evaluation, immunohistochemical staining and multiplex immunofluorescence.</p><p><strong>Results: </strong>Histopathological examination identified both classical and uncommon morphological characteristics, such as multinucleated giant cells, hemangiopericytoma-like vascular patterns, calcification and haemosiderosis. Immunohistochemical expression of programmed cell death ligand 1 (PD-L1) was rare, with only two cases showing focal positivity. Multiplex immunofluorescence for the analysis of the tumour immune microenvironment revealed distinct immune landscapes between PC and SCO. SCO exhibited a higher proportion of cytotoxic T lymphocytes (CTLs) and closer spatial interactions between macrophages and interferon (IFN)-γ-producing cells, reflecting a more robust antitumour immune response. In contrast, PC showed an increased proportion of exhausted CD8+ T cells, suggesting a more pronounced immunosuppressive microenvironment.</p><p><strong>Conclusions: </strong>This study reveals distinct immune microenvironmental profiles between PC and SCO, with SCO exhibiting an immune-active phenotype, whereas PC is characterised by features of immune exhaustion. These differences underscore the potential for differential immunotherapeutic approaches, such as targeting immune exhaustion pathways in PC or enhancing CTLs activity in SCO.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 4","pages":"e70029"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591797","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":"Detection of Human Prion Seeding Activity in Formalin-Fixed Paraffin-Embedded Archival Tissues.","authors":"Soňa Baranová, Radoslav Matěj, Jiri G Safar, Karel Holada","doi":"10.1111/nan.70028","DOIUrl":"10.1111/nan.70028","url":null,"abstract":"<p><strong>Aims: </strong>Formalin-fixed paraffin-embedded (FFPE) samples, routinely used in neuropathology, represent an invaluable resource for studying rare diseases like transmissible spongiform encephalopathies (TSE). Despite fixation-induced protein cross-linking, prion seeding activity can be effectively detected using the seeding amplification assays. In this study, we employed the second-generation real-time quaking-induced conversion (RT-QuIC) assay to analyse and quantify human prion seeding activity in FFPE brain tissues.</p><p><strong>Methods: </strong>FFPE frontal brain tissues were deparaffinised in xylene, followed by rehydration through descending concentrations of ethanol. The prion seeding activity in tissue homogenates was assessed by RT-QuIC assay utilising short recombinant hamster prion protein (rHaPrP90-231) as a substrate.</p><p><strong>Results: </strong>A total of 60 samples, including 30 cases of confirmed TSE, comprising both sporadic and genetic forms, as well as 30 non-TSE controls, were analysed. Prion seeding activity has been detected in all TSE samples except one sCJD (VV2) and one GSS (P102L) case, corresponding to an assay sensitivity of 93.3%. Conversely, we did not detect any RT-QuIC positivity in the control group, resulting in 100% specificity. The mean 50% prion seeding dose of FFPE sporadic TSE samples was 10^7.8/g of brain tissue.</p><p><strong>Conclusion: </strong>Our study emphasises high sensitivity and specificity of RT-QuIC assay for prion detection in archival human FFPE brain tissues and demonstrates its diagnostic reliability comparable to other tissue types even after years of storage. The applicability of FFPE samples in RT-QuIC assays facilitates retrospective diagnostics and provides logistical advantages for sample preservation and transportation.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 4","pages":"e70028"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591798","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":"Standardised TruAI Automated Quantification of Intracellular Neuromelanin Granules in Human Brain Tissue Sections.","authors":"Anastasia Filimontseva, Thais Cuadros, Zac Chatterton, Amy Burke, Anahid Ansari Mahabadian, Joan Compte, YuHong Fu, Miquel Vila, Glenda M Halliday","doi":"10.1111/nan.70033","DOIUrl":"10.1111/nan.70033","url":null,"abstract":"<p><strong>Aims: </strong>To standardise and automate the quantitation of human-unique neuromelanin granules in catecholamine neurons in post-mortem tissue sections from healthy individuals at different ages to understand any changes in these granules with age.</p><p><strong>Methods: </strong>Five- to 6-μm-thick fixed and paraffin-embedded transverse midbrain tissue sections were supplied from 47 cases from three brain banks following ethical approvals. Sections were prepared and automated digital images acquired. Standardisation and automation of the quantification of neuromelanin granules was performed using the TruAI feature of the Olympus VS200 desktop platform. Comparisons between stained and unstained sections as well as correlations with age were performed.</p><p><strong>Results: </strong>The automated platform reliably identified both stained and unstained intracellular neuromelanin granules and extracellular pigments, showing high reproducibility in measurements across laboratories using different tissue processing methods. Extraneuronal pigments were significantly smaller than intracellular neuromelanin granules. Sections processed for haematoxylin and eosin staining impacted the size and colour of both neuromelanin and the neurons containing neuromelanin. Haematoxylin made neuromelanin bluer, and the increased tissue processing made the intracellular area occupied by neuromelanin smaller in younger people. There was an increase in neuromelanin optical density and colour change (browner) with age.</p><p><strong>Conclusions: </strong>The TruAI automated platform reliably quantifies individual neuromelanin granules in catecholamine neurons. Extraneuronal pigments are considerably smaller in size than intracellular neuromelanin, and intracellular neuromelanin changes its properties with age. The darkening and colour change of intracellular neuromelanin suggest an increase in eumelanin over time in healthy individuals. These changes can be reliably identified using the automated platform.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 4","pages":"e70033"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822131","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}