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皮质pTDP-43纳入形态的异质性在肌缩侧面硬化症中

Rachel H Tan^1,2, Heather McCann³, Claire E Shepherd³

¹Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. rachel.tan1@sydney.edu.au.

Acta neuropathologica communications

|November 14, 2023

概括

这项研究基于运动皮层中的蛋白质聚合模式确定了三种不同的TDP-43病理 (ALS-TDP) 的肌缩性侧面硬化症亚型. 这些发现表明ALS-TDP不是单一的疾病,可以指导向治疗的发展.

科学领域:

神经病理学神经病理学
神经退行性疾病神经退行性疾病
蛋白质病变是一种蛋白质病变.

背景情况:

肌缩性侧面硬化症 (ALS) 涉及到异质的皮质酸化-TDP-43 (pTDP-43) 含物.
病态亚分类的ALS是罕见的,特别是在没有前性痴呆症 (FTD) 的病例中.
了解ALS中的pTDP-43亚型对于改善诊断和治疗至关重要.

研究的目的:

在没有FTD的ALS患者中调查皮质pTDP-43亚型的模式和相关性.
根据pTDP-43的总体形态和组成建立ALS的神经病理亚分类.

主要方法:

在61例没有FTD的ALS病例中检查了皮质pTDP-43聚合物.
根据pTDP-43和p62免疫组织化学分类的亚型:ALS-TDP类型E (颗粒状神经元含物,GFNI,p62-阴性),ALS-TDP类型B (神经元细胞质含物,NCIs,p62-阳性) 和ALS-TDP类型SC (稀有的皮质聚合物).
利用定量分析和主要成分分析来区分亚型和评估疾病特征.

主要成果:

确定了三种不同的ALS-TDP亚型:E型 (18%),B型 (67%) 和SC型 (15%).
类型E的pTDP-43 GFNI和谷物负担显著更高,地形分布更大 (较高的ALS-TDP阶段).
类型SC的病例患有阿尔茨海默氏症和勒维体病的患病率较高,认知分数较低.

结论:

在神经病理上,ALS-TDP是异质的,而不是单一的同质实体.
建议将pTDP-43和p62分为三种不同的亚型 (E,B,SC) 的分类,使用标准的运动皮层免疫组织化学来对待pTDP-43和p62.
在未来的研究中指定pTDP-43亚型将有助于更好地了解临床表型,并有助于针对蛋白质病变的向疗法开发.

关键词:

肌缩性侧面硬化症 (AMLS) 是一种疾病.前側葉退化前側葉退化 pTDP-43 的时间.

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