Risk and protective effects of the APOE gene towards Alzheimer's disease in the Kungsholmen project: variation by age and sex.

Abstract

BACKGROUND:

The risk effect of APOE epsilon 4 allele for Alzheimer's disease is acknowledged, whereas the putative protective effect of epsilon 2 allele remains in debate.

OBJECTIVES:

To investigate whether those inconsistent findings may be attributable to differences in age and sex composition of the study populations.

METHODS:

A community dementia free cohort (n = 985) aged > or =75 years was followed up to detect Alzheimer's disease cases (DSM-III-R criteria). Data were analysed using Cox models with adjustment for major potential confounders.

RESULTS:

Over a median 5.6 year follow up, Alzheimer's disease was diagnosed in 206 subjects. Compared with APOE epsilon 3/epsilon 3 genotype, the relative risk (RR) of Alzheimer's disease was 1.4 (95% confidence interval (CI), 1.0 to 2.0; p = 0.03) for heterozygous epsilon 4 allele and 3.1 (95% CI, 1.6 to 5.9) for homozygous epsilon 4 allele. The association between epsilon 4 allele and Alzheimer's disease risk was stronger in men than in women (RR related to the interaction term epsilon 4 allele by sex, 0.4; 95% CI, 0.2 to 0.9). The epsilon 4 allele accounted for one third of Alzheimer's disease cases among men, but only one tenth among women. The epsilon 2 allele was related to a reduced Alzheimer's disease risk mainly in people aged <85 years (RR, 0.4; 95% CI, 0.2 to 0.8). The RR of Alzheimer's disease related to the interaction term of epsilon 2 allele by age was 2.4 (95% CI, 1.0 to 6.0; p = 0.06).

CONCLUSIONS:

The APOE genotype specific effects on Alzheimer's disease vary by age and sex, in which the epsilon 4 allele has a stronger risk effect in men, and the epsilon 2 allele confers a protective effect only in younger-old people.

• Authors: C Qiu, M Kivipelto, H Agüero-Torres, B Winblad, L Fratiglioni
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 75 Issue 6 Pg. 828-33 (Jun 2004) ISSN: 0022-3050 [Print] England
• PMID: 15145993 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein E2
• Apolipoproteins E

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (epidemiology, genetics)
• Apolipoprotein E2
• Apolipoproteins E (genetics)
• Cohort Studies
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease (genetics, prevention & control)
• Genetic Testing
• Genetic Variation
• Genotype
• Humans
• Male
• Proportional Hazards Models
• Risk Factors
• Sex Factors
• Sweden (epidemiology)