Department of Psychology, Rowan University, 201 Mullica Hill Road, Glassboro, NJ, 08028, USA.
Department of Pathology and Cell Biology, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
Alzheimers Res Ther. 2020 Nov 4;12(1):141. doi: 10.1186/s13195-020-00712-4.
Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer's disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4-) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4- AD patients. On the other hand, APOE4- AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4- AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations.
载脂蛋白 E (APOE) 的 ε4 等位基因是散发性阿尔茨海默病 (AD) 的主要遗传风险因素。虽然研究人员已经广泛研究了 APOE ε4 (APOE4) 对 AD 易感性的影响，但很少有研究调查 APOE4 携带者与非携带者 AD 患者的表型差异。为了了解这些差异，我们对 APOE4 阳性 (APOE4+) 与 APOE4 阴性 (APOE4-) AD 患者之间报告的认知和病理差异进行了定性系统文献回顾。迄今为止，针对这一主题进行的研究表明，APOE4 不仅是 AD 易感性的重要介导物，而且可能在 AD 表现中赋予特定的表型异质性。具体而言，与 APOE4- AD 患者相比，APOE4+ AD 患者的内侧颞叶中似乎有更多的 tau 积累和脑萎缩，导致更大的记忆障碍。另一方面，与 APOE4+ AD 患者相比，APOE4- AD 患者的额叶和顶叶中似乎有更多的 tau 积累和脑萎缩，导致执行功能、视觉空间能力和语言方面的更大损害。尽管还需要更多的工作来验证和探究这些发现，但这些关于 APOE4+ 与 APOE4- AD 患者之间的病理和认知异质性的初步观察结果表明，与 APOE 基因型相关的 AD 表现存在根本分歧，这可能对这两种患者群体的治疗治疗具有重要意义。
