Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.
Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.
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DOI：
10.1038/s41380-020-0838-x
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发表时间：
2021-10
影响因子：
11
通讯作者：
Fox NC
中科院分区：
文献类型：
--
作者：
O'Connor A;Karikari TK;Poole T;Ashton NJ;Lantero Rodriguez J;Khatun A;Swift I;Heslegrave AJ;Abel E;Chung E;Weston PSJ;Pavisic IM;Ryan NS;Barker S;Rossor MN;Polke JM;Frost C;Mead S;Blennow K;Zetterberg H;Fox NC
血液生物标志物在推进阿尔茨海默病（AD）的临床护理和加速试验方面具有巨大的潜力。血浆磷酸化tau181 （p-tau181）是一种很有前景的血液生物标志物，然而，尚不清楚其水平是否在症状前AD中升高。因此，在一项家族性AD （FAD）纵向研究中，我们使用来自70个个体的153份血液样本来研究p-tau181变化的时间。血浆p-tau181测量，使用内部单分子阵列分析。我们比较了症状携带者、症状前携带者和非携带者之间的p-tau181，调整了年龄和性别。我们检查了p-tau181与神经丝光、估计到症状发生的年数（EYO）以及有症状亚组到实际发病的年数之间的关系。此外，我们研究了p-tau181与临床严重程度之间的关系，并测试了遗传亚群之间的差异。24例为症状前携带者（平均基线EYO - 9.6年），27例为非携带者。与非携带者相比，有症状和症状前突变携带者血浆p-tau181浓度均高于无症状携带者（p< 0.001）。血浆p-tau181显示出相当大的个体差异，但个体值区分了症状携带者（AUC 0.93 [95% CI 0.85 ~ 0.98]）和症状前携带者（EYO≥-7年）（AUC 0.86 [95% CI 0.72 ~ 0.94]）与相同年龄和性别的非携带者。从拟合模型中，有证据（p= 0.050）表明，在估计症状发作前16年，突变携带者的p-tau181浓度高于非携带者。我们发现血浆p-tau181浓度在症状性和症状前FAD中升高，这表明它可能是一种易于获取的AD病理生物标志物。
Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer’s disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house Single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. Additionally, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9·6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p<0·001) and presymptomatic mutation carriers (p<0·001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0·93 [95% CI 0·85−0·98]) and presymptomatic (EYO ≥ -7 years) (AUC 0·86 [95% CI 0·72−0·94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p=0·050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.
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DOI：
10.1038/s41582-018-0079-7
发表时间：
2018-11
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Hampel H;O'Bryant SE;Molinuevo JL;Zetterberg H;Masters CL;Lista S;Kiddle SJ;Batrla R;Blennow K
通讯作者：
Blennow K
影响因子：
48
作者：
Ryan, Natalie S.;Nicholas, Jennifer M.;Fox, Nick C.
通讯作者：
Fox, Nick C.
影响因子：
11.1
作者：
Mattsson N;Schöll M;Strandberg O;Smith R;Palmqvist S;Insel PS;Hägerström D;Ohlsson T;Zetterberg H;Jögi J;Blennow K;Hansson O
通讯作者：
Hansson O
影响因子：
9.9
作者：
McDade, Eric;Wang, Guoqiao;Bateman, Randall J.
通讯作者：
Bateman, Randall J.
影响因子：
9.9
作者：
Ryman, Davis C.;Acosta-Baena, Natalia;Bateman, Randall J.
通讯作者：
Bateman, Randall J.