JAMA Neurol:KL-VSHET+基因型与较低的阿尔茨海默病风险

2020-04-14 MedSci原创 MedSci原创

基因型KL-VSHET+携带者的阿尔茨海默病风险较低,与其相关信号通路研究有望成为治疗AD的新靶点

识别与载脂蛋白e4(APOE4)等位基因相互作用的遗传因素,可降低阿尔茨海默病(AD)的发病风险,加速寻找新的AD药物靶点。Klotho VS杂合子(KL-VSHET+状态)可防止衰老相关表型和认知能力下降,但其对携带APOE4的个体的作用尚不清楚。近日研究人员考察了APOE4携带者KL-VSHET+状态是否与AD风险降低和β-淀粉样蛋白(Aβ)病理学改变有关。

研究收集了25个独立的病例对照、基于家庭的和纵向的AD队列参与者数据,按APOE4状态分层,基因数据可从高密度单核苷酸变异微阵列获得。研究的主要终点为轻度认知障碍(MCI)或AD风险。

36530名参与者中,13782名患者不符合条件未纳入终点研究。参与者为60岁及以上,非西班牙裔,具有西北欧血统,分为认知正常、患有MCI或AD。研究发现,基因型KL-VSHET+与60岁或60岁以上携带APOE4的个体的AD风险降低相关(比值比为0.75),这一现象在60-80岁时更为显著(比值比为0.69)。此外,携带KL-VS杂合子的APOE4携带者转化为MCI或AD的风险降低(危险比为0.64)。最后,在APOE4携带者且年龄在60-80岁的对照组中,KL-VS杂合度与CSF中较高的Aβ和PET扫描中较低的Aβ相关。

研究发现,基因型KL-VSHET+携带者的阿尔茨海默病风险较低,与其相关信号通路研究有望成为治疗AD的新靶点。

原始出处:

Michael E. Belloy et al. Association of Klotho-VS Heterozygosity With Risk of Alzheimer Disease in Individuals Who Carry APOE4.JAMA Neurol. April 13, 2020.

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    2020-05-01 yinhl1978
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    2020-04-14 旺医

    顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息

    0

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