Brain:血浆Aβ42/40和磷酸化-tau217有助于预测阿尔茨海默病病理预后

2021-11-03 MedSci原创 MedSci原创

血浆Aβ42/40和磷酸化-tau217可能在临床实践、研究和药物开发中作为未来阿尔茨海默病病理预后标志物有用。

越来越多的人认识到,阿尔茨海默病的病理生理学是一个高度复杂和动态的过程,开始于淀粉样蛋白-β的早期积累,随后是tau沉积和神经退行性变这些病变可通过脑脊液分析、PET和MRI检测。然而,尽管这些技术在临床上是有用的,但它们是侵入性的、昂贵的或耗时的,这限制了它们在临床实践中的使用或它们在同一个人的可用性因此,迫切需要能够克服这些局限性的血液生物标记物,这些生物标记物可以广泛应用于初级保健以及检测阿尔茨海默病病理的临床试验。目前尚不清楚血浆生物标志物是否可以作为独立的预后工具来预测与早期阿尔茨海默病相关的变化。

Joana B Pereira等在BRAIN杂志发表研究文章,通过评估血浆生物标志物是否可以预测非痴呆个体中淀粉样蛋白负荷、tau蛋白积累、脑萎缩和认知的变化来解决这个问题。

该研究测定了来自瑞典BioFINDER-2研究的159名非痴呆患者、123名阿尔茨海默病痴呆患者和35名非阿尔茨海默病痴呆患者的血浆淀粉样蛋白-β 42/40 (a β42/40)、磷酸化tau181、磷酸化tau217和神经丝轻链。所有被试接受了纵向淀粉样蛋白(18F- flutemamol)和tau蛋白(18F-RO948) PET、结构MRI (T1加权)和认知测试。

单变量线性混合效应模型显示,血浆生物标志物与成像和认知测量之间有几个显著的关联。然而,当所有的生物标志物被纳入相同的多元线性混合效应模型时,低基线血浆Aβ42/40独立地预测了纵向淀粉样蛋白-PET信号的增加(P = 0.012),

血浆Aβ42/40水平独立预测非痴呆个体的纵向淀粉样蛋白- PET沉积。

tau-PET信号的增加,高血浆磷酸化tau217可独立预测脑萎缩和认知功能恶化(P<0.004)。

血浆P-tau217水平独立预测非痴呆个体中tau的纵向积累。

这些生物标志物的表现与脑脊液中检测到的相应生物标志物一样好或更好。

此外,它们表现出与使用约登指数定义的二元血浆生物标志物值相似的性能,这在临床中更容易实现。另外该研究发现,血浆Aβ42/40和磷酸化-tau217并不能预测非阿尔茨海默氏神经退行性疾病患者的纵向变化。

总之,基线血浆Aβ42/40和P-tau217水平是阿尔茨海默病病程中发生的病理变化的独立预测因子。血浆Aβ42/40和P-tau217可以作为临床实践中评估疾病进展的重要预后工具,从而在未来的临床试验中实现更准确的患者管理和更好的疾病监测。

原文出处

Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects, Brain, Volume 144, Issue 9, September 2021, Pages 2826–2836, https://doi.org/10.1093/brain/awab163

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    2022-09-06 feifers
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    2021-11-04 hb2008ye
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    2021-11-04 膀胱癌

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