Relationships between biomarkers in aging and dementia
Relationships between biomarkers in aging and dementia
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DOI：
10.1212/wnl.0b013e3181bc010c
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发表时间：
2009-10-13
期刊：
影响因子：
9.9
通讯作者：
Mathis, C. A.
中科院分区：
文献类型：
--
作者：
Jagust, W. J.;Landau, S. M.;Mathis, C. A.
背景资料：使用[F-18]氟脱氧葡萄糖（FDG）和[C-11]匹兹堡化合物B（PI B）的PET成像已被提议作为阿尔茨海默病（AD）的生物标志物，42个氨基酸的β-淀粉样蛋白（A β（1-42））和总tau和磷酸化tau（t-tau和p-tau）的CSF测量也是如此。生物标志物和疾病严重程度之间的关系是不完全understood.Methods：10例AD患者，11例对照组和34例轻度认知功能障碍的阿尔茨海默病神经影像学倡议进行了临床评估; CSF测量A β（1-42），t-tau，和p-tau;和PIB-PET和FDG-PET扫描。使用连续回归和二分结果对数据进行分析，根据AD患者和其他队列对照的截止值，将受试者分为AD“阳性”或“阴性”。二分分类显示PIB-PET和CSF A β（1-42）测量之间存在实质性一致性（91%一致性，kappa = 0.74），PIB-PET和p-tau之间的适度一致性（76%一致性，kappa = 0.50），以及其他比较的最小一致性（kappa < 0.3）。简易精神状态检查评分与FDG-PET显著相关，但与PIB-PET或CSF A β无关（1-42）。经诊断校正的回归模型显示，PIB-PET与A β（1-42）、t-tau和p-tau（181 p）显著相关，而FDG-PET仅与A β（1-42）相关。[F-18]氟脱氧葡萄糖-PET与其他生物标志物适度相关，但与认知相关性更好。阿尔茨海默病的不同生物标志物提供彼此不同的信息，这些信息可能是互补的。神经病学（R）2009; 73：1193-1199
Background: PET imaging using [F-18]fluorodeoxyglucose (FDG) and [C-11]Pittsburgh compound B (PIB) have been proposed as biomarkers of Alzheimer disease (AD), as have CSF measures of the 42 amino acid beta-amyloid protein (A beta(1-42)) and total and phosphorylated tau (t-tau and p-tau). Relationships between biomarkers and with disease severity are incompletely understood.Methods: Ten subjects with AD, 11 control subjects, and 34 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative underwent clinical evaluation; CSF measurement of A beta(1-42), t-tau, and p-tau; and PIB-PET and FDG-PET scanning. Data were analyzed using continuous regression and dichotomous outcomes with subjects classified as "positive" or "negative" for AD based on cutoffs established in patients with AD and controls from other cohorts.Results: Dichotomous categorization showed substantial agreement between PIB-PET and CSF A beta(1-42) measures (91% agreement, kappa = 0.74), modest agreement between PIB-PET and p-tau (76% agreement, kappa = 0.50), and minimal agreement for other comparisons (kappa < 0.3). Mini-Mental State Examination score was significantly correlated with FDG-PET but not with PIB-PET or CSF A beta(1-42). Regression models adjusted for diagnosis showed that PIB-PET was significantly correlated with A beta(1-42), t-tau, and p-tau(181p), whereas FDG-PET was correlated only with A beta(1-42).Conclusions: PET and CSF biomarkers of A beta agree with one another but are not related to cognitive impairment. [F-18]fluorodeoxyglucose-PET is modestly related to other biomarkers but is better related to cognition. Different biomarkers for Alzheimer disease provide different information from one another that is likely to be complementary. Neurology (R) 2009; 73: 1193-1199