Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer's disease. Neurology 2003 Jan 28;60(2):246-52
Date
01/29/2003Pubmed ID
12552039DOI
10.1212/01.wnl.0000042478.08543.f7Scopus ID
2-s2.0-0037469076 (requires institutional sign-in at Scopus site) 228 CitationsAbstract
OBJECTIVE: To test the hypothesis that the APOE epsilon4 allele is associated with the clinical manifestations of AD through an association with the pathologic hallmarks of disease.
METHODS: Participants were older Catholic nuns, priests, and brothers who agreed to annual neurologic and neuropsychological evaluation for AD and other common neurologic conditions and brain autopsy at the time of death. There were 77 persons without dementia and 51 with probable AD; 38 participants had one or more epsilon4 alleles.
RESULTS: In logistic regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with the likelihood of clinical AD (odds = 3.46, 95% CI = 1.44 to 8.33). However, controlling for the effect of AD pathology, the association of the epsilon allele with clinical AD was reduced by >50% and was no longer significant (odds = 1.58, 95% CI = 0.56 to 4.43). Similarly, in linear regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with level of cognitive function proximate to death (regression coefficient = -0.477, p = 0.005). However, after controlling for the effect of AD pathology, the association of the epsilon4 allele with level of cognition was reduced by >80% and was no longer significant (regression coefficient = -0.093). Similar results were found in analyses using separate measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles, and in analyses of five different cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability).
CONCLUSIONS: The APOE epsilon4 allele appears to be associated with the clinical manifestations of AD through an association with the pathologic hallmarks of AD rather than another mechanism.
Author List
Bennett DA, Wilson RS, Schneider JA, Evans DA, Aggarwal NT, Arnold SE, Cochran EJ, Berry-Kravis E, Bienias JLMESH terms used to index this publication - Major topics in bold
Age FactorsAged
Aged, 80 and over
Alleles
Alzheimer Disease
Apolipoprotein E4
Apolipoproteins E
Brain
Cognition Disorders
Disease Progression
Educational Status
Female
Genetic Predisposition to Disease
Humans
Linear Models
Logistic Models
Longitudinal Studies
Male
Memory Disorders
Neuropsychological Tests
Odds Ratio
Risk Factors