Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, 901 E Willetta Street, Phoenix, AZ, 85006, USA.
University of Arizona, 714 E Van Buren Street, Phoenix, AZ, 85006, USA.
Nat Commun. 2020 Feb 3;11(1):667. doi: 10.1038/s41467-019-14279-8.
Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease.
载脂蛋白 E4（APOE4）等位基因每增加一个拷贝，患阿尔茨海默病痴呆的风险就会更高，而 APOE2 等位基因则与阿尔茨海默病痴呆的风险较低相关，但目前尚不清楚 APOE2 纯合子是否具有特别低的风险。我们在 5000 多例具有临床特征和神经病理学特征的阿尔茨海默病病例和对照中生成了阿尔茨海默病的优势比和其他发现。与 APOE2/3 和 3/3 相比，APOE2/2 与阿尔茨海默病的低优势比相关，与 APOE4/4 相比，优势比极低，并且 APOE2 和 APOE4 基因剂量的影响在神经病理学确认组中明显大于 24000 多例未经神经病理学确认的病例和对照组。发现并针对 APOE 及其变体影响阿尔茨海默病的因素，可能会对理解、治疗和预防该疾病产生重大影响。
