Testing Meningiomas With Methylation Arrays: Insights and Recommendations From a Large Single-Centre Study

使用甲基化芯片检测脑膜瘤：一项大型单中心研究的见解与建议

Meningiomas are common primary CNS tumours, and their morphological diagnosis is usually straightforward. Their histological grading according to CNS WHO criteria alone provides limited information on recurrence risk. Risk stratification of meningiomas combining WHO grade, methylation class and copy number profile improves prediction of the risk of early recurrence. Because of the frequency of meningiomas in diagnostic practice, applying this prediction algorithm to all meningiomas is financially not viable in most healthcare systems. Our data suggest that Grade 2 and 3 meningiomas should be prioritised for methylation profiling. A small proportion of Grade 1 meningiomas may also benefit from integrated molecular analysis, and further research is needed to explore if those histologically benign meningiomas with a predicted increased recurrence risk are associated with distinct demographic or histological characteristics.

脑膜瘤是常见的中枢神经系统（CNS）原发性肿瘤，其形态学诊断通常较为简单。仅依据中枢神经系统世界卫生组织（WHO）标准进行的组织学分级，在预测复发风险方面提供的信息有限。结合WHO分级、甲基化类别和拷贝数谱对脑膜瘤进行风险分层，可改善对早期复发风险的预测。由于脑膜瘤在诊断实践中较为常见，在大多数医疗体系中，对所有脑膜瘤应用这一预测算法在经济上不可行。我们的数据表明，应优先对2级和3级脑膜瘤进行甲基化分析。一小部分1级脑膜瘤也可能从综合分子分析中获益，还需要进一步研究，以探讨那些在组织学上呈良性但预测复发风险增加的脑膜瘤，是否与独特的人口统计学或组织学特征相关。

REF: Ruiz F, Rispoli R, Jaunmuktane Z, et al. Testing Meningiomas With Methylation Arrays: Insights and Recommendations From a Large Single-Centre Study. Neuropathol Appl Neurobiol. 2025;51(3):e70018. doi:10.1111/nan.70018 PMID: 40356449

Alpha-Synuclein as a Potential Biomarker for Inclusion Body Myositis in Blood and Muscle

α-突触核蛋白作为血液和肌肉中包涵体肌炎的潜在生物标志物

Diagnosis of inclusion body myositis (IBM) is difficult and currently based on a combination of clinical and (immuno)histological findings. Biomarkers facilitating the diagnostic process are needed. Alpha-synuclein (αSN) aggregates are a known histological feature of IBM, but there is a lack of information on their diagnostic relevance. Furthermore, serum αSN concentrations in IBM have not been investigated. αSN reactivity may serve as an additional immunohistochemical marker for IBM diagnosis. Furthermore, this study indicates that αSN serum concentrations decrease with disease duration and clinical deterioration. Therefore, serum αSN may be provisionally considered a monitoring biomarker in IBM, pending further studies.

包涵体肌炎（IBM）的诊断颇具难度，目前主要依据临床和（免疫）组织学检查结果的综合判断。因此，需要有能够辅助诊断过程的生物标志物。α-突触核蛋白（αSN）聚集体是已知的IBM组织学特征，但关于其诊断相关性的信息却十分匮乏。此外，尚未有针对IBM患者血清αSN浓度的研究。αSN反应性可能作为IBM诊断的一项额外免疫组织化学标志物。此外，本研究表明，血清αSN浓度会随着疾病病程延长和临床症状恶化而降低。因此，在进一步研究结果出炉之前，血清αSN可暂时被视为IBM的一种监测生物标志物。

REF: Mayer T, Scholle L, Foerster L, et al. Alpha-Synuclein as a Potential Biomarker for Inclusion Body Myositis in Blood and Muscle. Neuropathol Appl Neurobiol. 2025;51(3):e70019. doi:10.1111/nan.70019 PMID: 40384347

Collablots: Quantification of Collagen VI Levels and Its Structural Disorganisation in Cell Cultures From Patients With Collagen VI-Related Dystrophies

胶原绘图法：定量分析胶原蛋白 VI 相关肌营养不良症患者细胞培养物中胶原蛋白 VI 水平及其结构紊乱情况

This study aims to develop a quantitative method for assessing collagen VI expression in cell cultures, which is crucial for the diagnosis and treatment of collagen VI-related dystrophies. The collablot assay represents a suitable method for quantifying collagen VI expression and its organisation in culture and assessing the effect of therapies.

本研究旨在开发一种定量方法，用于评估细胞培养物中胶原蛋白VI的表达情况，这对于胶原蛋白VI相关肌营养不良症的诊断和治疗至关重要。胶原蛋白印迹测定法是一种合适的方法，可用于量化培养物中胶原蛋白VI的表达及其组织情况，并评估治疗效果。

REF: Osegui-Barcenilla N, Sendino M, Martín-González S, et al. Collablots: Quantification of Collagen VI Levels and Its Structural Disorganisation in Cell Cultures From Patients With Collagen VI-Related Dystrophies. Neuropathol Appl Neurobiol. 2025;51(3):e70020. doi:10.1111/nan.70020 PMID: 40400418

MYL1-Related Congenital Myopathy: Clinical, Genetic and Pathological Insights

MYL1相关先天性肌病：临床、遗传和病理学见解

Congenital myopathies and congenital muscular dystrophies encompass heterogeneous clinical and genetic groups of disorders characterised by muscle weakness with antenatal or early postnatal onset. These conditions are categorised according to distinctive myopathological features and causative genes. Despite advances in diagnosis through massive parallel sequencing and progress in understanding the underlying pathogenesis, many aspects of these disorders remain poorly understood. MYL1-related congenital myopathy is an ultra-rare and severe condition, associated with a deficiency of essential/alkali light myosin and impaired development of fast-twitch type II muscle fibres. This study aims to advance the understanding of the phenotype and pathogenesis of MYL1-congenital myopathy. We analysed the clinical characteristics of two individuals harbouring three novel variants in the MYL1 gene. We conducted detailed genomic analysis and extensive studies on their muscles using histological, immunohistochemical, immunofluorescence, Western Blot and electron microscopy. Both individuals showed a very severe congenital myopathy, characterised by congenital hypotonia and weakness, requiring ventilatory and nutritional assistance. Muscle biopsy revealed dystrophic-like or myopathic changes, with notable smallness of fast-twitch type II fibres, often arranged around larger type I fibres, drawing a floret pattern. These fibres expressed developmental myosin and exhibited features of aberrant myofibrillogenesis. Type I myofibres exhibited correct sarcomere alignment, but like the small fast-twitch fibres, both showed distorted cell organelles, vacuolar aggregates and membranous debris, indicating autophagic impairment. Our findings confirm that bi-allelic MYL1 variants are associated with a severe congenital myopathy, characterised by a distinctive clinical and histopathological phenotype involving impaired type II fibre development. Additionally, our study reveals a role for MYL1 in the organisation and trophism of all muscle fibre types. SUMMARY: MYL1 biallelic variants cause severe congenital myopathy with early hypotonia and type II fibre hypotrophy. Muscle biopsy shows a distinct pattern, including floret-like fibre arrangement. Findings suggest a broader role for MYL1 in fibre organisation and autophagy across muscle fibre types.

先天性肌病和先天性肌营养不良症涵盖了临床和遗传学上异质性的疾病群体，其特征为产前或产后早期出现的肌无力。这些疾病根据独特的肌病理特征和致病基因进行分类。尽管通过大规模平行测序在诊断方面取得了进展，且在理解潜在发病机制方面也有进步，但这些疾病的许多方面仍知之甚少。MYL1相关先天性肌病是一种极为罕见且严重的疾病，与必需/碱性肌球蛋白轻链缺乏以及快肌II型肌纤维发育受损有关。本研究旨在增进对MYL1相关先天性肌病的表型和发病机制的理解。我们分析了两名携带MYL1基因三个新变异体个体的临床特征。我们进行了详细的基因组分析，并使用组织学、免疫组织化学、免疫荧光、蛋白质印迹和电子显微镜对他们的肌肉进行了广泛研究。两名患者均表现出非常严重的先天性肌病，特征为先天性肌张力低下和肌无力，需要通气和营养支持。肌肉活检显示出类似肌营养不良或肌病的改变，快肌II型纤维明显变小，常围绕较大的I型纤维排列，形成花簇样图案。这些纤维表达发育性肌球蛋白，并表现出肌原纤维生成异常的特征。I型肌纤维的肌节排列正常，但与小的快肌纤维一样，两者均显示细胞器扭曲、空泡聚集体和膜性碎片，提示自噬功能受损。我们的研究结果证实，MYL1双等位基因变异与严重的先天性肌病相关，其特征为独特的临床和组织病理学表型，涉及II型纤维发育受损。此外，我们的研究揭示了MYL1在所有肌纤维类型的组织和营养维持中的作用。总结：MYL1双等位基因变异导致严重的先天性肌病，早期出现肌张力低下和II型纤维萎缩。肌肉活检显示出独特的模式，包括花簇样纤维排列。研究结果表明MYL1在各种肌纤维类型的纤维组织和自噬中具有更广泛的作用。

REF: Madrigal I, Villar-Vera C, Arca G, et al. MYL1-Related Congenital Myopathy: Clinical, Genetic and Pathological Insights. Neuropathol Appl Neurobiol. 2025;51(3):e70025. doi:10.1111/nan.70025 PMID: 40488356

Lecanemab Binds to Transgenic Mouse Model-Derived Amyloid-β Fibril Structures Resembling Alzheimer's Disease Type I, Type II and Arctic Folds

lecanemab（仑卡奈单抗）可结合类似于阿尔茨海默病 I 型、II 型和北极型折叠的转基因小鼠模型来源的淀粉样蛋白 - β 纤维结构

Lecanemab, an Alzheimer's disease US Food and Drug Administration-approved monoclonal antibody, was previously reported to have a high affinity against intermediately sized amyloid-β aggregates. Subsequently, it was observed by immunogold labelling that lecanemab can also bind to human type I amyloid-β fibrils. To determine whether lecanemab binds to amyloid-β fibril structures other than type I, we analysed its binding capacity to various structurally defined and pathologically relevant amyloid-β fibrils. These findings may also explain the low incidence of ARIA-E with lecanemab in clinical trials. This is because human meningeal amyloid-β fibrils derived from cerebral amyloid angiopathy affected brain tissue also contain a fixed and ordered N-terminus, most likely preventing lecanemab binding.

仑卡奈单抗是一种获美国食品药品监督管理局批准用于治疗阿尔茨海默病的单克隆抗体，此前有报道称其对中等大小的β-淀粉样蛋白聚集体具有高亲和力。随后，通过免疫金标记观察到，仑卡奈单抗还能与人类I型β-淀粉样蛋白纤维结合。为确定仑卡奈单抗是否能结合除I型以外的β-淀粉样蛋白纤维结构，我们分析了它与各种结构明确且具有病理相关性的β-淀粉样蛋白纤维的结合能力。这些发现也可能解释了在临床试验中使用仑卡奈单抗时淀粉样蛋白相关影像学异常水肿（ARIA - E）发生率较低的原因。这是因为源自受脑淀粉样血管病影响的脑组织的人类脑膜β-淀粉样蛋白纤维也有固定且有序的N端，很可能会阻止仑卡奈单抗的结合。

REF: Peralta Reyes FS, Sommerhage S, Willbold D, Schröder GF, Gremer L. Lecanemab Binds to Transgenic Mouse Model-Derived Amyloid-β Fibril Structures Resembling Alzheimer's Disease Type I, Type II and Arctic Folds. Neuropathol Appl Neurobiol. 2025;51(3):e70022. doi:10.1111/nan.70022 PMID: 40495448