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The British Journal of Psychiatry (2000) 176: 468-472
© 2000 The Royal College of Psychiatrists

APOE {epsilon}4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome

SHOUMITRO DEB, FRCPsych, JOHN BRAGANZA, MRCPsych, NADINE NORTON, BSc, HYWEL WILLIAMS, BSc, PATRICK G. KEHOE, PhD, JULIE WILLIAMS, PhD and MICHAEL OWEN, FRCPsych

Division of Psychological Medicine, University of Wales College of Medicine, Cardiff

Declaration of interest This study was partly funded by the Medical Research Council (grant no. 9810900).

Correspondence: Dr S. Deb, Division of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4xN. Tel: 01222 562323. Fax: 0122 555047. E-mail Deb{at}Cardiff.ac.uk

Background Recent studies of the relationship between the apolipoprotein E (APOE) gene and Alzheimer's disease in adults with Down's syndrome have revealed inconsistent results.

Aims To assess the role of the APOE gene in the manifestation of Alzheimer's disease in adults with Down's syndrome.

Method We studied the APOE genotypes of 24 adults with dementia and 33 non-demented adults with Down's syndrome over 35 years of age, and an additional group of 164 non-learning disabled adults. We also carried out a meta-analysis of all previously published studies of association between APOE and Down's syndrome, incorporating the current data.

Results We observed a non-significant excess of APOE {epsilon}4 and a reduction of {epsilon}2 in adults with dementia compared with non-demented adults with Down's syndrome in our sample. However, meta-analysis showed a significantly higher frequency of {epsilon}4 in adults with dementia compared with non-demented adults with Down's syndrome (odds ratio=2.02, 95% Cl 1.33-3.07, P=0.001), but no significant reduction in the frequency of {epsilon}2.

Conclusions The APOE {epsilon}4 allele acts as a risk factor for the age-specific manifestation of Alzheimer's disease in people with Down's syndrome.




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