@article{3c4a9ab2429842b4b9a310e63f2cfdb3,
title = "APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort",
abstract = "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.",
author = "Sandra Weintraub and Merilee Teylan and Benjamin Rader and Chan, {Kwun C.G.} and Mark Bollenbeck and Kukull, {Walter A.} and Christina Coventry and Emily Rogalski and Eileen Bigio and Mesulam, {M. Marsel}",
note = "Funding Information: Study funded by grants from the National Institute of Neurologic Disorders and Stroke (NS085770), the National Institute on Deafness and Other Communication Disorders (R01 DC008552), National Institute of Neurologic Diseases and Stroke (R01 NS075075), and the National Institute on Aging (AG013854, AGO56258). The NACC database is funded by NIA/NIH grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Funding Information: This project was supported by DC008552 from the National Institute on Deafness and Communication Disorders; AG13854 (Alzheimer Disease Core Center) and AG056258 from the National Institute on Aging; NS075075 from the National Institute of Neurological Disorders and Stroke (NINDS). Publisher Copyright: {\textcopyright} American Academy of Neurology.",
year = "2020",
month = feb,
day = "11",
doi = "10.1212/WNL.0000000000008666",
language = "English (US)",
volume = "94",
pages = "E607--E612",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",
}