title: ApoE E4 is a susceptibility factor in amnestic but not aphasic dementias.
abstract: The goal of this study was to determine if the apolipoprotein ε gene, which is a well-established susceptibility factor for Alzheimer disease (AD) pathology in typical amnestic dementias, may also represent a risk factor in the language-based dementia, primary progressive aphasia (PPA). Apolipoprotein E genotyping was obtained from 149 patients with a clinical diagnosis of PPA, 330 cognitively healthy individuals (NC), and 179 patients with a clinical diagnosis of probable Alzheimer's disease (PrAD). Allele frequencies were compared among the groups. Analyses were also completed by sex and in 2 subsets of PPA patients: 1 in which the patients were classified by subtype (logopenic, agrammatic, and semantic) and another in which pathologic data were available. The allele frequencies for the PPA group (ε2:5%, ε3:79.5%, and ε4:15.4%) showed a distribution similar to the NC group, but significantly different from the PrAD group. The presence of an ε4 allele did not influence the age of symptom onset or aid in the prediction of AD pathology in PPA. These data show that ε4 polymorphism, which is a well-known risk factor for AD pathology in typical amnestic dementias, has no similar relationship to the clinical syndrome of PPA or its association with AD pathology.
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. erogalski@gmail.com
authors.forename: Emily Joy
authors.initials: EJ
authors.lastname: Rogalski
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Harrison
authors.forename: Irene
authors.initials: I
authors.lastname: Helenowski
authors.forename: Nancy
authors.initials: N
authors.lastname: Johnson
authors.forename: Eileen
authors.initials: E
authors.lastname: Bigio
authors.forename: Manjari
authors.initials: M
authors.lastname: Mishra
authors.forename: Sandra
authors.initials: S
authors.lastname: Weintraub
authors.forename: Marek-Marsel
authors.initials: MM
authors.lastname: Mesulam
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D018888:Aphasia, Primary Progressive / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053327:Apolipoprotein E4