Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
Alzheimers Res Ther. 2012 Jun 14;4(3):20. doi: 10.1186/alzrt123.
With the recent interest in Alzheimer's disease course modification and earlier, even preclinical, intervention, questions have arisen regarding the potentially confounding impact of apolipoprotein E (APOE) genotype on study design, therapeutic outcomes, and even clinical practice. APOE e4 carriers have a faster rate of cognitive decline both preclinically and during the mild cognitive impairment (MCI) stage, and a higher burden of cerebrovascular amyloid that may be the basis for the observed gene-dose-related increased frequency of immunomodulatory therapy-induced meningoencephalitis and cerebral microhemorrhages. To date, this has impacted study design in some research trials but not clinical practice.
随着人们对阿尔茨海默病病程修正和更早、甚至临床前干预的兴趣日益浓厚，关于载脂蛋白 E（APOE）基因型对研究设计、治疗结果甚至临床实践可能产生的潜在混杂影响的问题已经出现。APOE e4 携带者在临床前和轻度认知障碍（MCI）阶段的认知衰退速度更快，脑血管淀粉样蛋白负担也更高，这可能是观察到基因剂量相关免疫调节治疗诱导的脑膜炎和脑微出血频率增加的基础。迄今为止，这已影响到一些研究试验的研究设计，但尚未影响到临床实践。
