APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort

Sandra Weintraub*, Merilee Teylan, Benjamin Rader, Kwun C.G. Chan, Mark Bollenbeck, Walter A. Kukull, Christina Coventry, Emily Rogalski, Eileen Bigio, M. Marsel Mesulam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


ObjectiveTo compare the proportion of APOE ϵ4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD).MethodThe proportion of APOE 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 APOE ϵ4 carrier status, adjusting for age at onset and sex as needed.ResultsUsing NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOE 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 APOE 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.ConclusionThe proportion of APOE ϵ4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOE 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.

Original languageEnglish (US)
Pages (from-to)E607-E612
Issue number6
StatePublished - Feb 11 2020

ASJC Scopus subject areas

  • Clinical Neurology


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