APOE ε4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome

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 nondemented 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=0.01), 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. Declaration of interest This study was partly funded by the Medical Research Council (grant no. 98 10900).