血清粉样蛋白P成分作为神经退行性疾病中药物标的遗传证据
A Floriaan Schmidt1,2,3,4, Chris Finan1,2,4, Sandesh Chopade1,2
1Institute of Cardiovascular Science, Faculty of Population Health, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
Open biology
|July 16, 2024
概括
血清粉样蛋白P成分 (SAP) 与神经退行和痴呆风险有关. 遗传分析显示,较高的SAP水平与阿尔茨海默氏症和勒维体痴呆症有关,这表明SAP是一个潜在的治疗目标.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学是一种遗传学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 在阿尔茨海默病 (AD) 和其他痴呆症中驱动神经元死亡的机制仍然不清楚.
- 血清粉样蛋白P成分 (SAP) 是一种血蛋白,对神经元具有细胞毒性,并促进粉样蛋白斑块和神经纤维细胞的形成.
- 通常被排除在大脑之外,增加SAP暴露与更高的痴呆风险相关,新皮质SAP水平与痴呆症严重程度有关.
研究的目的:
- 为了研究血清粉样蛋白P成分 (SAP) 和神经退行之间的因果遗传联系.
- 评估基因决定的血SAP度与神经退行性疾病的关联.
主要方法:
- 三项涉及44288名参与者的全基因组关联研究的元分析.
- 西斯-门德尔随机化分析,以评估基因仪器化血SAP与神经退行性疾病之间的关联.
- 对与血陶度相关性的评估.
主要成果:
- 较高的基因仪器血SAP度与阿尔茨海默病风险增加显著相关 (OR1.07,p=1.8×10−3).
- 高血SAP水平也与勒维体痴呆症 (OR1.37,p=1.5×10−5) 和高血tau度 (0.06 log2(ng l−1),p=4.55×10−6) 有关.
- 这些遗传发现支持SAP的神经病原作用.
结论:
- 遗传证据强烈表明血清粉样蛋白P成分 (SAP) 在神经退行过程中起因作用.
- 通过药物miridesap从血液和大脑中减少SAP,可能提供一种对痴呆症的神经保护策略.
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