CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer's disease.
CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer's disease.
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DOI：
10.1523/jneurosci.3785-09.2010
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发表时间：
2010-02-10
期刊：
影响因子：
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通讯作者：
Alzheimer's Disease Neuroimaging Initiative
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作者：
Fjell AM;Walhovd KB;Fennema-Notestine C;McEvoy LK;Hagler DJ;Holland D;Brewer JB;Dale AM;Alzheimer's Disease Neuroimaging Initiative
脑萎缩以及淀粉样β蛋白（Aβ42）和微管相关蛋白tau的脑脊液水平改变是阿尔茨海默病（AD）相关病理的有效生物标志物。然而，脑脊液生物标志物与脑形态测量之间的关系知之甚少。因此，我们探讨了以下问题：（1）脑脊液生物标志物水平能否解释正常对照组（NC）与轻度认知障碍（MCI）患者或AD患者之间的形态测量差异？（2）脑脊液生物标志物与全脑萎缩有何关系？（3）脑脊液生物标志物和形态测量与临床变化（临床痴呆评定量表总和[CDR - sb]）的相关性有多密切？对来自阿尔茨海默病神经影像学倡议的370名参与者（105名NC / 175名MCI / 90名AD）进行了研究，其中309人随访了1年，176人随访了2年。分析在整个皮质表面以及30个皮质和皮质下感兴趣区域（ROIs）进行。结果显示，脑脊液生物标志物水平不能解释基线时脑形态测量的组间差异，但脑脊液生物标志物水平与许多脑区的纵向萎缩率有中等程度的关系，且不限于内侧颞叶结构。基线形态测量对萎缩的预测能力至少与脑脊液生物标志物相同。即使Aβ42水平与对照组相当且磷酸化tau水平低于对照组的MCI患者，其萎缩程度也比对照组更严重。形态测量对CDR - sb变化的预测优于脑脊液生物标志物。这些结果表明，MCI和AD中的形态测量变化并非脑脊液生物标志物变化的继发结果，且这两种类型的生物标志物提供了互补信息。
Brain atrophy and altered CSF-levels of amyloid beta (Aβ42) and the microtubule-associated protein tau are potent biomarkers of Alzheimer's Disease (AD) related pathology. However, the relationship between CSF biomarkers and brain morphometry is poorly understood. Thus, we addressed the following questions: (1) Can CSF biomarker levels explain the morphometric differences between normal controls (NC) and patients with mild cognitive impairment (MCI) or AD? (2) How are CSF biomarkers related to atrophy across the brain? (3) How closely are CSF biomarkers and morphometry related to clinical change (CDR sum of boxes [CDR-sb])? 370 participants (105 NC/ 175 MCI/ 90 AD) from the Alzheimer's Disease Neuroimaging Initiative were studied, of whom 309 were followed for one and 176 for two years. Analyses were performed across the entire cortical surface, as well as for 30 cortical and subcortical regions of interest (ROIs). Results showed that CSF biomarker levels could not account for group differences in brain morphometry at baseline but that CSF biomarker levels showed moderate relationships to longitudinal atrophy rates in numerous brain areas, not restricted to medial temporal structures. Baseline morphometry was at least as predictive of atrophy as were CSF biomarkers. Even MCI patients with levels of Aβ42 comparable to controls and of p-tau lower than controls showed more atrophy than the controls. Morphometry predicted change in CDR-sb better than did CSF biomarkers. These results indicate that morphometric changes in MCI and AD are not secondary to CSF biomarker changes, and that the two types of biomarkers yield complementary information.