back to Fifth International Conference
Estrogen, Apolipoprotein E and the
Risk of Alzheimer's Disease
C.M. van Duijn,* H. Meijer, J.C.M. Witteman, L.M.
Havekes, P. de Knijff, C. Van Broeckhoven and A. Hofman
Department of Epidemiology & Biostatistics, Erasmus
University Medical School, Rotterdam, The Netherlands;
TNO, Institute of Prevention and Health, Gaubius Laboratory,
Leiden, The Netherlands; Neurogenetics Laboratory, Born
Bunge Foundation, Dep of Biochemistry, University of Antwerp,
Estrogen may have a beneficial effect on the risk and course of Alzheimer's
disease (AD) through several mechanisms including improvement of cerebral
blood flow, stimulation of the neuron or gliacyte and interaction with genetic
factors. We have studied the relationship of estrogen replacement therapy
and age at menopause to the risk of AD and the role of genetic factors in
Patients (N=124) were derived from a population-based study of early-onset
AD (<65 years). All cases met the NINCDS-ADRDA criteria for probable
AD. Each patient was matched randomly to an age and sex matched population
control. Data on family and medical history were collected by an informant
interview for cases and controls. Family history was verified by a sibling.
Data of affected and unaffected relatives of 19 cases from families with
autosomal dominant AD were collected according to the same protocol.
A history of estrogen replacement therapy was found less often for patients
than controls (odds ratio (OR) 0.40; 95% confidence interval (CI): 0.19-0.91).
A significant difference was found only in patients carrying the APOE*4
allele (OR 0.14; 95% CI 0.02-0.87). No significant association was found
in APOE3E3 or APOE*2 carriers. An early age at menopause (<47 years)
was associated with a significantly increased risk of AD in those with a
positive family history of disease (OR 4.07; 95% CI: 1.07-15.40). A similar
trend was found in APOE*4 carriers. When comparing affected and unaffected
relatives of cases with autosomal dominant AD, age at menopause was on average
2.6 years earlier in affected relatives (SE 0.67; p<0.05).
Our study suggests a protective effect of estrogen on the risk of AD through
the interaction with APOE and other genetic factors.