载脂蛋白 E 预测认知正常衰老中的淀粉样-β 但不能预测 tau 阿尔茨海默病病理学。
APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging.
机构信息
Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
出版信息
Ann Neurol. 2010 Jan;67(1):122-31. doi: 10.1002/ana.21843.
OBJECTIVE
To examine interactions of apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging.
METHODS
Two hundred forty-one cognitively normal individuals, aged 45-88 years, had cerebral amyloid imaging studies with Pittsburgh Compound-B (PIB). Of the 241 individuals, 168 (70%) also had cerebrospinal fluid (CSF) assays of amyloid-beta(42) (Abeta(42)), tau, and phosphorylated tau (ptau(181)). All individuals were genotyped for APOE.
RESULTS
The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age-dependent manner from 0% at ages 45-49 years to 30.3% at 80-88 years. Reduced levels of CSF Abeta(42) appeared to begin earlier (18.2% of those aged 45-49 years) and increase with age in higher frequencies (50% at age 80-88 years) than elevations of MCBP. There was a gene dose effect for the APOE4 genotype, with greater MCBP increases and greater reductions in CSF Abeta(42) with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF Abeta(42) levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau(181).
INTERPRETATION
Increasing cerebral Abeta deposition with age is the pathobiological phenotype of APOE4. The biomarker sequence that detects Abeta deposition may first be lowered CSF Abeta(42), followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD.
目的
研究载脂蛋白 E（APOE）基因型与年龄以及与认知正常衰老过程中体内阿尔茨海默病（AD）前期指标的相互作用。
方法
241 名认知正常者，年龄 45-88 岁，进行了匹兹堡化合物-B（PIB）脑淀粉样蛋白成像研究。在 241 名个体中，有 168 名（70%）还进行了脑脊液（CSF）中淀粉样蛋白-β（42）（Abeta（42））、tau 和磷酸化 tau（ptau（181））的检测。所有个体均进行了 APOE 基因型检测。
结果
具有 PIB 平均皮质结合潜力（MCBP）升高的个体频率呈年龄依赖性增加，从 45-49 岁年龄组的 0%增加到 80-88 岁年龄组的 30.3%。CSF Abeta（42）水平的降低似乎更早开始（45-49 岁年龄组中有 18.2%），并且随着年龄的增加，频率增加（80-88 岁年龄组中有 50%）。APOE4 基因型存在基因剂量效应，随着 APOE4 等位基因数量的增加，MCBP 增加更明显，CSF Abeta（42）减少更明显。携带 APOE2 等位基因的个体随着年龄的增长，MCBP 没有增加，CSF Abeta（42）水平高于没有 APOE2 等位基因的个体。APOE4 或 APOE2 对 CSF tau 或 ptau（181）没有影响。
结论
随着年龄的增长，大脑中 Abeta 沉积的增加是 APOE4 的病理生物学表型。检测 Abeta 沉积的生物标志物序列可能首先是 CSF Abeta（42）降低，然后是 PIB 的 MCBP 升高。相当一部分认知正常者存在疑似的前期 AD。
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