From Mesulam Center for Cognitive Neurology and Alzheimer's Disease (S.W., B.R., C.C., E.R., E.B., M.-M.M.) and the Departments of Psychiatry and Behavioral Sciences (S.W., E.R.), Pathology (E.B.), and Neurology (M.-M.M.), Northwestern Feinberg School of Medicine, Chicago, IL; and Department of Epidemiology, National Alzheimer Coordinating Center (M.T., M.B., W.A.K.), and Department of Biostatistics (K.C.G.C.), University of Washington, Seattle.
Neurology. 2020 Feb 11;94(6):e607-e612. doi: 10.1212/WNL.0000000000008666. Epub 2019 Nov 8.
To compare the proportion of ε4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD).
The proportion of ε4 carriers was compared among the following 3 groups: (1) 42 patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core; (2) 1,418 patients with autopsy-confirmed AD and amnestic dementia of the Alzheimer type (DAT/AD); and (3) 2,608 cognitively normal controls (NC). The latter 2 groups were compiled from the National Alzheimer Coordinating Center database. Logistic regression models analyzed the relationship between groups and ε4 carrier status, adjusting for age at onset and sex as needed.
Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be ε4 carriers. Adjusting for sex and age at symptom onset, the DAT/AD group was 2.46 times as likely to be carriers compared to PPA/AD. There was no significant difference in the proportion of ε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and 8 either mixed (n = 5) or too severe (n = 3) to subtype. The proportion of carriers and noncarriers was similar for logopenic and agrammatic subtypes, both having fewer carriers.
The proportion of ε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that ε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather than language-related neocortices.
比较 ɛ4 基因型携带者在失语症与遗忘型阿尔茨海默病（AD）中的比例。
在以下 3 组中比较 ɛ4 携带者的比例：（1）西北 AD 中心临床核心纳入的 42 名原发性进行性失语症（PPA）和 AD 病理（PPA/AD）患者；（2）1418 名经尸检证实的 AD 和遗忘型 AD 患者；（3）2608 名认知正常对照者（NC）。后两组由国家 AD 协调中心数据库编译。使用逻辑回归模型分析组间关系和 ɛ4 携带状态，根据需要调整发病年龄和性别。
使用 NC 作为参考，调整性别和年龄，DAT/AD 组更有可能成为 ɛ4 携带者，其几率是 NC 的 3.97 倍。调整性别和症状发病年龄，DAT/AD 组成为携带者的几率是 PPA/AD 的 2.46 倍。与 NC 相比，PPA/AD 组中 ɛ4 携带者的比例无显著差异。PPA 亚型包括 24 名失读症、10 名语法性非流利型和 8 名混合型（n=5）或严重型（n=3），无法亚型化。失读症和语法性非流利型两种亚型的携带者和非携带者比例相似，两者携带者都较少。
在遗忘型 AD 而非失语症表现中， ɛ4 携带者的比例升高。这些结果表明， ɛ4 是一种解剖选择性风险因素，优先增加与记忆相关的内侧颞叶区域对 AD 病理的易感性，而不是与语言相关的新皮质。
