Annals of Neurology:血清中细胞骨架生物标志物可预测长期认知功能下降

2021-01-17 Freeman MedSci原创

血清中细胞骨架生物标志物可预测长期认知功能下降

 
在症状前期的散发性阿尔茨海默病(AD)和进展到临床型AD中,发现有前途的血液生物标志物可以为治疗试验的被试提供选择、筛选和风险分层,并作为不良临床结果的预测标志物。然而,这些血液标志物作为微创、性价比高的工具,用于研究临床AD基础的神经退行性过程,却很少受到关注。
 
对这些生物标志物的进一步了解,会改善疾病发展过程中的早期预防和治疗策略。血液中的总tau(t-tau)、神经丝轻链蛋白(Nf-L)和胶质纤维酸性蛋白(GFAP)是值得关注的细胞骨架生物标志物,。血浆t-tau与认知能力下降、海马体积和神经纤维缠结有关,血清Nf-L与家族性AD的发病有关。此外,GFAP也与AD和认知障碍有关。然而,对于这些生物标志物如与长期的认知表现有何关系:比如,临床AD的时间依赖性发展,以及认知功能和脑形态的长期变化,目前了解得较少。
 
藉此,加州大学的Kumar B. Rajan等人Chicago Health and Aging Project (CHAP)队列,探究了tau, NfL,GFAP与AD和认知功能下降直接的关系。
他们利用单分子阵列技术,在1327名参与者(60%为非洲裔美国人和女性)的人群样本中,对血清中t-tau、Nf-L和GFAP的浓度进行了超敏免疫测定,这些参与者都进行了AD的临床评估,完成了认知评估,并进行了1.5T结构磁共振成像。
 
结果显示:较高浓度的血清生物标志物与临床AD的发展相关;尤其是时间特异性关联显著:血清生物标志物与16年内认知能力下降较快相关;基线t-tau>0.40pg/ml的人下降速度快30%,Nf-L>25.5pg/ml的人下降速度快110%,GFAP>232pg/ml的人与最低四分之一的人相比下降速度快130%。基线GFAP>232pg/ml的参与者与数值<160pg/ml的参与者相比,海马体积下降速度快160%。此外,基线t-tau越高,第三脑室体积增加越快,基线Nf-L和GFAP与皮质厚度下降越快有关。
 
这个研究的重要意义在于,发现了血清t-tau、Nf-L和GFAP可以预测散发性AD的发展和认知能力下降,以及脑结构特征的变化,表明它们不仅可以作为筛选和预测性生物标志物,而且可以解释阿尔茨海默痴呆症的发病机制
 
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    2021-07-15 yinhl1978
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    2021-01-22 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2021-01-17 wxl882001

    了解

    0