Cognition and neuroanatomy differed between carriers and non-carriers of the e4 allele of the apolipoprotein E gene in a study that compared the phenotypic expression of the allele in people with mild Alzheimer's disease.
“We found the presence or absence of the APOE e4 allele influences the cognitive and anatomic phenotypic expression of AD in a dissociable manner,” concluded Dr. David A. Wolk of the University of Pennsylvania, Philadelphia, and his coauthors in the Alzheimer's Disease Neuroimaging Initiative.
The results “have important implications for the early detection and monitoring of AD, because APOE carrier status seems to exert a strong influence on the cognitive and anatomic expression of the disease” (Proc. Natl. Acad. Sci. U.S.A. 2010 May 17 [doi: 10.1073/pnas.1001412107]).
The e4 allele is “the major genetic risk factor” for AD and is one of the three major alleles of the APOE gene, which codes for a lipid transport protein. Previously available data on the association between APOE allele carrier status and phenotypic differences have varied or have been inconsistent, according to the investigators.
To address concerns over possible misdiagnoses, Dr. Wolk included cerebrospinal fluid testing data to improve the accuracy of the diagnosis of Alzheimer's disease in the study's 67 e4 carriers and 24 noncarriers.
The APOE e4 carriers had significantly greater impairments in delayed recall as well as recognition memory and memory retention. In comparison, non-carriers showed significantly greater impairments in tests of working memory, executive control, and lexical access.
In a statement from the university, Dr. Wolk's co-author, Dr. Bradford Dickerson of Massachusetts General Hospital, Boston, referred to recent studies describing differences in the way in which Alzheimer's patients responded to drugs, based on whether they had the APOE e4 allele or not. “Rather than restricting trials exclusively to patients with or without APOE e4, the results suggest that different behavioral and brain measures might be a useful approach to consider in evaluating investigational drugs,” he said.
Disclosures: The authors had no conflicts of interest to disclose. The study was primarily funded by the ADNI, which is funded by the National Institute of Aging and the National Institute of Biomedical Imaging and Bioengineering, and the Foundation for the National Institutes of Health, through contributions from several pharmaceutical companies.