轻度认知障碍患者脑脊液生物标志物的预测及纵向研究
Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.
作者信息
Brys Miroslaw, Pirraglia Elizabeth, Rich Kenneth, Rolstad Sindre, Mosconi Lisa, Switalski Remigiusz, Glodzik-Sobanska Lidia, De Santi Susan, Zinkowski Ray, Mehta Pankaj, Pratico Domenico, Saint Louis Leslie A, Wallin Anders, Blennow Kaj, de Leon Mony J
机构信息
New York University School of Medicine, NY, USA.
出版信息
Neurobiol Aging. 2009 May;30(5):682-90. doi: 10.1016/j.neurobiolaging.2007.08.010. Epub 2007 Sep 24.
OBJECTIVES
To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
METHODS
A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau(231)), amyloid beta (Abeta) Abeta(42)/Abeta(40) ratio, isoprostane (IP) as well as P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios.
RESULTS
At baseline and at follow-up MCI-AD showed higher levels P-tau(231), T-tau, IP, P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios and lower Abeta(42)/Abeta(40) than MCI-MCI or NL-NL. Baseline P-tau(231) best predicted MCI-AD (80%, p<0.001) followed in accuracy by P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios (both 75%, p's<0.001), T-tau (74%, p<0.001), Abeta(42)/Abeta(40) (69%, p<0.01), and IP (68%, p<0.01). Only IP showed longitudinal effects (p<0.05).
CONCLUSIONS
P-tau(231) is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.
目的
纵向评估从轻度认知障碍（MCI）转变为阿尔茨海默病（AD）过程中的五种脑脊液（CSF）生物标志物。
方法
对86名受试者进行基线及2年随访的临床和脑脊液研究，其中包括22名从MCI进展为AD的患者（MCI-AD）、43名未恶化的MCI患者（MCI-MCI）和21名对照者（NL-NL）。对所有受试者检测总tau蛋白和磷酸化tau蛋白（T-tau、P-tau(231)）、淀粉样β蛋白（Aβ）、Aβ(42)/Aβ(40)比值、异前列腺素（IP）以及P-tau(231)/Aβ(42/40)和T-tau/Aβ(42/40)比值。
结果
在基线和随访时，MCI-AD组的P-tau(231)、T-tau、IP、P-tau(231)/Aβ(42/40)和T-tau/Aβ(42/40)比值水平高于MCI-MCI组或NL-NL组，而Aβ(42)/Aβ(40)比值低于MCI-MCI组或NL-NL组。基线时P-tau(231)对MCI-AD的预测能力最强（80%，p<0.001），其次是P-tau(231)/Aβ(42/40)和T-tau/Aβ(42/40)比值（均为75%，p<0.001）、T-tau（74%，p<0.001）、Aβ(42)/Aβ(40)（69%，p<0.01）和IP（68%，p<0.01）。只有IP显示出纵向变化（p<0.05）。
结论
P-tau(231)是MCI向AD转变的最强预测指标。IP水平独特地显示出纵向进展效应。这些结果提示脑脊液生物标志物可用于二级预防试验。
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