Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark; Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark; Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark.
Alzheimers Dement. 2018 Jan;14(1):71-80. doi: 10.1016/j.jalz.2017.05.006. Epub 2017 Aug 22.
In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established.
Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively.
In observational analyses risk of Alzheimer's disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10 and 9 × 10). APOE-weighted allele scores were associated with stepwise decreases in apoE (P for trend, <1 × 10). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27-1.57) for Alzheimer's disease and 1.33 (1.25-1.43) for all dementia (F-statistics = 3821).
Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.
在最近的前瞻性研究中，载脂蛋白 E (apoE) 的血浆水平较低与痴呆风险增加相关。然而，这是否反映了因果关系仍有待确定。
我们使用孟德尔随机化方法，分别在观察性和遗传分析中研究了来自普通人群的 106562 人和 75260 人。
在观察性分析中，阿尔茨海默病和所有痴呆的风险随着 apoE 水平的逐步降低而呈阶梯式增加（趋势检验 P 值均为 2×10 和 9×10）。APOE 加权等位基因评分与 apoE 的逐步降低相关（趋势检验 P 值均<1×10）。在工具变量分析中，遗传决定的 apoE 每降低 1mg/dL 的因果风险比为 1.41（1.27-1.57），用于阿尔茨海默病和所有痴呆（F 统计量=3821）。
遗传上和终身apoE 水平较低与普通人群中痴呆的高风险相关。观察性和遗传估计之间的一致性表明存在潜在的因果关系。
