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 ε4 and a reduction of ε2 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 ε4 in adults with dementia compared with non-demented adults with Down's syndrome (odds ratio=2.02, 95% CI 1.33-3.07, P=0.001), but no significant reduction in the frequency of ε2. Conclusions: The APOE ε4 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. 9810900).