A POLYMORPHISM IN THE REGULATORY REGION OF APOE ASSOCIATED WITH RISK FOR ALZHEIMERS DEMENTIA

The epsilon 4 allele of the apolipoprotein E gene (APOE) has been asso ciated with an increased risk of developing Alzheimer's disease (AD; r efs 1,2). However, it is apparent that the APOE epsilon 4 allele alone is neither necessary nor sufficient to cause the disease(3-5). We hav e recently found three new polymorphisms within the APOE transcription al regulatory region (M.J.A. et al., manuscript submitted) and now est ablish an association between one of these polymorphisms (-491A/T) and dementia as observed in Cases Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a comm on variant (-491A) is associated with increased risk for AD, and that this association is independent of APOE epsilon 4 status. In vitro stu dies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.