衰老与痴呆症中生物标志物之间的关系。
Relationships between biomarkers in aging and dementia.
作者信息
Jagust W J, Landau S M, Shaw L M, Trojanowski J Q, Koeppe R A, Reiman E M, Foster N L, Petersen R C, Weiner M W, Price J C, Mathis C A
机构信息
Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94620, USA.
出版信息
Neurology. 2009 Oct 13;73(15):1193-9. doi: 10.1212/WNL.0b013e3181bc010c.
BACKGROUND
PET imaging using [(18)F]fluorodeoxyglucose (FDG) and [(11)C]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 (Abeta(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 Abeta(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 Abeta(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 Abeta(1-42). Regression models adjusted for diagnosis showed that PIB-PET was significantly correlated with Abeta(1-42), t-tau, and p-tau(181p), whereas FDG-PET was correlated only with Abeta(1-42).
CONCLUSIONS
PET and CSF biomarkers of Abeta agree with one another but are not related to cognitive impairment. [(18)F]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.
背景
使用[（18）F]氟脱氧葡萄糖（FDG）和[（11）C]匹兹堡化合物B（PIB）的PET成像已被提议作为阿尔茨海默病（AD）的生物标志物，脑脊液中42个氨基酸的β-淀粉样蛋白（Abeta（1-42））以及总tau蛋白和磷酸化tau蛋白（t-tau和p-tau）的检测指标也同样如此。生物标志物之间的关系以及它们与疾病严重程度的关系尚未完全明确。
方法
来自阿尔茨海默病神经影像学计划的10名AD患者、11名对照者以及34名轻度认知障碍患者接受了临床评估；检测了脑脊液中的Abeta（1-42）、t-tau和p-tau；并进行了PIB-PET和FDG-PET扫描。根据其他队列中AD患者和对照者确定的临界值，将受试者分类为AD“阳性”或“阴性”，使用连续回归和二分结果分析数据。
结果
二分法分类显示PIB-PET与脑脊液Abeta（1-42）检测结果之间有高度一致性（一致性为91%，kappa = 0.74），PIB-PET与p-tau之间有中等一致性（一致性为76%，kappa = 0.50），其他比较的一致性最小（kappa <0.3）。简易精神状态检查表评分与FDG-PET显著相关，但与PIB-PET或脑脊液Abeta（1-42）无关。经诊断调整的回归模型显示，PIB-PET与Abeta（1-42）、t-tau和p-tau（181p）显著相关，而FDG-PET仅与Abeta（1-42）相关。
结论
Abeta的PET和脑脊液生物标志物相互一致，但与认知障碍无关。[（18）F]氟脱氧葡萄糖-PET与其他生物标志物有一定相关性，但与认知的相关性更好。阿尔茨海默病的不同生物标志物提供了彼此不同但可能互补的信息。
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