JAMA子刊:利用血浆生物标志物检测唐氏综合征患者脑部Tau病理情况

2022-07-19 MedSci原创 MedSci原创

血浆p-tau217是DS中tau和Aβ脑部病理变化的一个非常准确的血液生物标志物,可以帮助指导疾病筛选。

新的血浆生物标志物,特别是磷酸化tau(p-tau),可以检测阿尔茨海默病的大脑tau聚集。为了确定哪些血浆生物标志物组合可以准确检测唐氏综合征(DS)的脑部tau病理变化,来自匹兹堡大学的学者开展了相关研究,结果发表在JAMA Neurology杂志上。

这是一项横断面、多中心的阿尔茨海默氏症生物标志物联盟-唐氏综合征研究,包括成年的DS患者和没有DS的兄弟姐妹的对照组。所有在入组时采集血浆、正电子发射断层扫描(PET)和认知情况。其中,收集患者血浆p-tau217、胶质纤维酸性蛋白(GFAP)、淀粉样β42/40(Aβ42/Aβ40)、神经丝光(NfL)和总tau(t-tau);tau正电子发射断层成像(tau-PET)和Aβ-PET。主要结果是Tau-PET状态。次要结果包括Aβ-PET状态和认知表现。

结果显示,在300名DS患者和37名非DS兄弟姐妹的对照组中,平均(SD)年龄为45.0(10.1)岁,167人(49.6%)为男性。在全部接受血浆p-tau217和GFAP分析的DS患者中,258人有其他血浆生物标志物数据,119人、213人和288人分别进行了tau-PET、Aβ-PET和认知评估。与A-T-DS相比,Aβ-PET阳性的tau-PET阳性(A+T+)DS和A+T-DS的血浆p-tau217和t-tau明显增加,而GFAP仅在A+T+DS中增加。A+T+DS的血浆p-tau217水平也明显高于A+T-DS。在患有DS的参与者中,血浆p-tau217和GFAP(但不是其他血浆生物标志物)在与年龄相关的模型中与异常的tau-PET和Aβ-PET状态持续相关(OR=1.59 -2.32)。

p-tau217和年龄的组合在检测颞部和新皮质区域的tau-PET异常时表现最好(AUC=0.96-0.99)。Aβ-PET状态的最合理模型包括p-tau217、t-tau和年龄(AUC=0.93-0.95)。在多变量模型中,较高的p-tau217水平而不是其他生物标志物与DS精神状态检查(β,-0.24,95% CI,-0.36至-0.12;P < .001)和诱导回忆试验(β,-0.40;95% CI,-0.53至-0.26;P < .001)的表现较差相关。

综上,血浆p-tau217是DS中tau和Aβ脑部病理变化的一个非常准确的血液生物标志物,可以帮助指导疾病筛选。

 

参考文献:

Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers. JAMA Neurol. Published online July 05, 2022. doi:10.1001/jamaneurol.2022.1740

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    2023-03-21 zhmscau
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    2022-07-20 hb2008ye
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    2022-07-19 医鸣惊人

    认真学习了

    0

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    2022-07-18 肿瘤克星

    JAMA上文章都是顶级的,谢谢梅斯及时上新

    0

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Alzheimer&Dementia:除了Aβ和tau蛋白,这些血浆蛋白也与认知能力下降和痴呆风险有关!

本研究在无痴呆症患者中发现了几种与认知能力下降和痴呆症的长期风险有关的血浆蛋白。

Neuorlogy:血浆基线总 tau 和神经丝轻链较高,则卒中风险较高

较高的血浆总 tau 和 NfL 水平与随后卒中的风险增加有关

JAMA NEURO:塞莫瑞单抗对轻度阿尔茨海默病及前驱疾病患者的安全性和疗效研究

由聚集的tau蛋白组成的神经纤维缠结是阿尔茨海默病(AD)的神经病理学标志之一,与临床疾病的严重程度相关。

JAMA子刊:临床前老年痴呆患者的皮质PET成像模式的差异性

早期tau沉积在临床前AD期间可能遵循多种轨迹,并可能涉及几个皮质区域。

拓展阅读

Alzheimer&Dementia:血浆 Aβ42/40 和认知变异性与认知功能有关

本研究结果将现有的研究结果扩展到了美国黑人样本,采用的方法成本低、负担小,可以在研究中心之外实施,从而支持了包容性注意力缺失症生物标志物研究的努力。

Science Bulletin:中科大申勇教授:基于血液的阿尔茨海默病生物标志物多中心横断面和纵向研究

这些结果还强调了 pTau 和 GFAP 作为早期检测和筛查注意力缺失症的非侵入性方法的潜力

BMC MED:宣武医院研究揭示ZDHHC21突变引起异常棕榈酰化促进家族性阿尔茨海默病

ZDHHC21 p.T209S是中国FAD血统中一个新的、候选的致病基因突变。

第99届美国神经病理学家协会年会:阿尔茨海默病中淀粉样蛋白低聚物的视网膜尸检分析

已确定的神经病理学分类AD分期(如Braak)的进展可能与视网膜寡聚体Aβ水平相关。

JAMA子刊:轻度认知障碍或痴呆症患者的Aβ-PET阳性率的种族和民族差异

MCI和痴呆患者中淀粉样蛋白PET阳性的种族和民族差异可能表明认知障碍潜在病因的差异

JAMA Neurology:针对阿尔兹海默症,罗氏Aβ单抗crenezumab临床再次失败!

Crenezumab的耐受性良好,但可能无法到达改善患者的临床痴呆综合汇总评定量表评分。