PAPER

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

C Qiu, M Kivipelto, H Agüero-Torres, B Winblad and L Fratiglioni

Ageing Research Centre, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and the Stockholm Gerontology Research Centre, Stockholm, Sweden

Correspondence to:
Correspondence to:
Dr C Qiu
Stockholm Gerontology Research Centre, Box 6401 (Olivecronas väg 4), S-113 82 Stockholm, Sweden; chengxuan.qiu{at}neurotec.ki.se

Background: The risk effect of APOE 4 allele for Alzheimer’s disease is acknowledged, whereas the putative protective effect of 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 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 3/3 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 4 allele and 3.1 (95% CI, 1.6 to 5.9) for homozygous 4 allele. The association between 4 allele and Alzheimer’s disease risk was stronger in men than in women (RR related to the interaction term 4 allele by sex, 0.4; 95% CI, 0.2 to 0.9). The 4 allele accounted for one third of Alzheimer’s disease cases among men, but only one tenth among women. The 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 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 4 allele has a stronger risk effect in men, and the 2 allele confers a protective effect only in younger-old people.

Keywords: Alzheimer’s disease; apolipoprotein E gene; population based study

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