Data from: ApoE is a correlate of phenotypic heterogeneity in Alzheimer's disease in a national cohort

Objective: To compare the proportion of APOEε4 genotype carriers in aphasic versus amnestic variants of Alzheimer's disease (AD). Method: The proportion of APOEε4 carriers was compared among 3 groups. 1) Forty-two 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); 3) 2,608 cognitively normal controls (NC). The latter two groups were compiled from the National Alzheimer Coordinating Center (NACC) database. Logistic regression models analyzed the relationship between groups and APOEε4 carrier status, adjusting for age of onset and sex as needed. Results: Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOEε4 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 APOEε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and eight either mixed (n=5) or too severe (n=3) to subtype. The proportion of carriers and non carriers was similar for logopenic and agrammatic subtypes, both having fewer carriers. Conclusion: The proportion of APOEε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOEε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather that language-related neocortices.