The apolipoprotein E (APOE) gene contains both the major common risk variant for late onset Alzheimer’s disease (AD), e4, and the major neuroprotective variant, e2. Here we examine the association of APOE e2 with multiple neurodegenerative pathologies, leveraging the NACC v. 10 database of 1557 brains that included 130 e2 carriers and 679 e4 carriers in order to examine potential neuroprotective effects. For AD-related pathologies of amyloid plaques and Braak stage, e2 had large and highly significant protective effects contrasted with e3/e3 and e4 carriers with odds ratios of about 0.50 for e3 contrasts and 0.10 for e4 contrasts. When we separately examined e2/e4 carriers, risk for AD pathologies was similar to that of e4 carriers, not e2 carriers. For multiple fronto-temporal lobar pathologies and tauopathies, e2 was not significantly associated with pathology. In sum, we found that e2 was associated with large but circumscribed protective effects.

载脂蛋白 E (APOE) 基因包含晚发性阿尔茨海默病 (AD) 的主要常见风险变异 e4 和主要神经保护变异 e2。在这里，我们利用包含 130 个 e2 携带者和 679 个 e4 携带者的 1557 个大脑的 NACC v.10 数据库检查 APOE e2 与多种神经退行性疾病的关联，以检查潜在的神经保护作用。对于淀粉样斑块和 Braak 阶段的 AD 相关病理，e2 与 e3/e3 和 e4 携带者相比具有大且非常显着的保护作用，e3 对比的优势比约为 0.50，e4 对比的优势比约为 0.10。当我们分别检查 e2/e4 携带者时，AD 病理的风险与 e4 携带者相似，而不是 e2 携带者。对于多发性额颞叶病变和 tauopathies，e2 与病理学没有显着相关性。总之，我们发现 e2 与大而有限的保护作用有关。