一种液体生物标志物揭示了TDP-43拼接抑制在前症状ALS-FTD中的损失
Katherine E Irwin1,2, Pei Jasin1, Kerstin E Braunstein1
1Department of Pathology, Johns Hopkins Medicine, Baltimore, MD, USA.
Nature medicine
|January 26, 2024
概括
失去了TARDNA结合蛋白43kDa (TDP-43) 拼接抑制发生在肌缩侧面硬化症和前性痴呆症 (ALS-FTD) 的早期,甚至在症状出现之前. 在血液或脑脊液中检测出隐形肝瘤衍生生成长因子类蛋白2 (HDGFL2) 可能作为早期诊断生物标志物.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 失去了TARDNA结合蛋白43kDa (TDP-43) 拼接抑制是肌缩侧面硬化症 (ALS) 和前性痴呆症 (FTD) 的标志.
- 在疾病早期,包括症状前阶段,这种异常的存在尚不清楚.
- 可以通过体液中的新表位体检测出暗示TDP-43功能丧失的隐形外子包容.
研究的目的:
- 在早期的ALS和FTD中调查TDP-43拼接抑制异常的发生情况.
- 评估隐秘肝瘤衍生的生生长因子样蛋白2 (HDGFL2) 新表位物作为ALS-FTD早期诊断生物标志物的潜力.
主要方法:
- 在HDGFL中开发和利用一种特定于TDP-43依赖的密码表位体的单克隆抗体2.
- 测量ALS-FTD患者脑脊液 (CSF) 和血液中的神秘HDGFL2水平,包括症状前C9orf72突变载体.
- 隐秘的HDGFL2水平与已确定的生物标记物的比较,例如神经纤维光纤和化神经纤维重链.
主要成果:
- 在ALS-FTD中观察到TDP-43拼接抑制的丧失,包括症状前的C9orf72突变载体.
- 与对照人群相比,在家族和零星ALS患者的CSF中发现了显著升高的神秘HDGFL2水平.
- 在家族性ALS中,神经纤维光纤和化神经纤维重链在CSF中的神秘HDGFL2升高之前.
- 在患有ALS-FTD的个体的血液中可以检测到神秘的HDGFL2,包括症状前的携带者,其水平与CSF度有很强的相关性.
结论:
- 丧失TDP-43密码拼接抑制是ALS-FTD的早期事件,甚至发生在症状前.
- 在CSF和血液中检测HDGFL2神秘的新表位体代表了早期ALS-FTD的有希望的诊断生物标志物.
- 这种生物标志物可以促进患者的早期诊断,临床试验的招募和治疗目标参与度的评估.
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