Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease.

Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease.
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了解细胞外TAU的复杂性有助于对阿尔茨海默氏病血液筛查的发展。

DOI:
10.1016/j.jalz.2018.09.010
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发表时间:
2019-03
期刊:
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子:
--
通讯作者:
Walsh DM
Walsh DM
中科院分区:
其他
文献类型:
--
作者:
Chen Z;Mengel D;Keshavan A;Rissman RA;Billinton A;Perkinton M;Percival-Alwyn J;Schultz A;Properzi M;Johnson K;Selkoe DJ;Sperling RA;Patel P;Zetterberg H;Galasko D;Schott JM;Walsh DM

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tau蛋白在阿尔茨海默病(AD)中起着核心作用,并且对测量血液和CSF中的tau有着巨大的兴趣。我们开发了一组免疫测定法,用于测量基于当前最佳临床和CSF生物标志物标准诊断的人类样本中的tau。在CSF中,中间区域检测到的和N-末端检测到的tau占主导地位,并在疾病中上升。在血浆中,N-末端测定(NT 1)检测到AD和AD-轻度认知障碍(MCI)中tau水平升高。血浆NT 1测量将发现队列和验证队列中的对照与AD-MCI(曲线下面积,AUC=0.88)和AD(AUC=0.96)分开(AUC分别为0.79和0.75)。CSF和血浆中tau的形式是不同的,但在每种标本类型中,AD中某些片段的水平增加。血浆NT 1 tau的测量应积极追求作为一个潜在的基于血液的筛选试验AD/AD-MCI。
The tau protein plays a central role in Alzheimer’s disease (AD) and there is huge interest in measuring tau in blood and CSF. We developed a set of immunoassays to measure tau in specimens from humans diagnosed based on current best clinical and CSF biomarker criteria. In CSF, mid-region-detected and N-terminal-detected tau predominated and rose in disease. In plasma, an N-terminal assay (NT1) detected elevated levels of tau in AD and AD-mild cognitive impairment (MCI). Plasma NT1 measurements separated controls from AD-MCI (area under the curve, AUC=0.88) and AD (AUC=0.96) in a Discovery Cohort; and in a Validation Cohort (with AUCs=0.79 and 0.75, respectively). The forms of tau in CSF and plasma are distinct, but in each specimen type the levels of certain fragments are increased in AD. Measurement of plasma NT1 tau should be aggressively pursued as a potential blood-based screening test for AD/AD-MCI.
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