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


OBJECTIVE
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.
Qiu
C
C
Ageing Research Centre, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and the Stockholm Gerontology Research Centre, Stockholm, Sweden. chengxuan.qui@neurotec.ki.se
Kivipelto
M
M
Agüero-Torres
H
H
Winblad
B
B
Fratiglioni
L
L
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053329:Apolipoprotein E2; D001057:Apolipoproteins E / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000517:prevention & control; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden / Q000453:epidemiology
D053329:Apolipoprotein E2; D001057:Apolipoproteins E