Cerebrospinal fluid β-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease:: The effect of APOE ε4 allele
Cerebrospinal fluid β-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease:: The effect of APOE ε4 allele
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DOI：
10.1016/j.biopsych.2004.07.021
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发表时间：
2004-11-01
影响因子：
10.6
通讯作者：
Cohen, RM
中科院分区：
文献类型：
--
作者：
Sunderland, T;Mirza, N;Cohen, RM
背景：脑脊液中β-淀粉样蛋白(1-42)和tau的测定与阿尔茨海默病(AD)的已知神经病理学有关。大量证据也表明，在19号染色体上至少有一个APOE epsilon 4等位基因的个体患AD的风险增加。我们在AD患者和健康的老年对照组中检测了这些脑脊液标志物，使用APOE epsilon4等位基因的缺失或存在作为预测变量，以寻找可能预测AD预后的生物标志物。我们评估了292名受试者(142名对照受试者和150名轻中度AD受试者)脑脊液中β-淀粉样蛋白(1-42)和总tau的水平，他们是国家精神卫生研究所的研究参与者。对照组中有AD家族史的受试者比例较高。所有受试者都接受了广泛的全球认知测试。当按是否存在apoE epsilon 4等位基因划分时，至少有一个epsilon 4等位基因的对照组的脑脊液β-淀粉样蛋白(1-42)水平显著低于未携带apoE等位基因的对照组(p<；0.01)，但tau水平无显著差异。与正常对照组比较，AD患者脑脊液中β-淀粉样蛋白(1-42)含量降低，tau含量升高(P<0.05)。
Background: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD.Methods. We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research, participants at the National Institute of Mental Health. The group of control subject was enriched with a high percentage of subjects with a positive family history of AD. All subject underwent extensive global cognitive testing.Results. When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE 64 allele (p < .01). As expected, the AD patients bad lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p