Abstract 17377: Plasma Levels of Apolipoprotein E and Risk of Dementia and Cerebrovascular Disease in the General Population
Background: The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for dementia and cerebrovascular disease. In contrast, it remains unclear whether plasma levels of apoE confer additional risk. We tested whether plasma levels of apoE associate with Alzheimer disease, all dementia, and cerebrovascular disease, independently of APOE genotype.
Methods: We included 76,386 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). We measured plasma apoE levels and calculated risk of disease according to age-and sex-adjusted percentile groups of plasma apoE concentrations: 0%-33, 34%-66%, and 67%-100%. We genotyped for rs429358 and rs7412, which combine into six common APOE genotypes (ε22, ε32, ε42, ε33, ε43, ε44).
Results: Multifactorially adjusted hazard ratios (HRs) increased from the highest (67%-100%) to the lowest (0%-33%) apoE percentile group for Alzheimer disease (p for trend=3.6x10-13) and for all dementia (p for trend=1.3x10-11), and remained significant after adjustment for APOE genotype (p for trends=0.006 and 0.03, respectively). Plasma levels of apoE were not associated with risk of cerebrovascular disease (p=0.52). In low-risk ε32+ε33 individuals and in high-risk ε43+ε44 individuals, multifactorially adjusted HRs increased from the highest (67%-100%) to the lowest (0%-33%) apoE percentile group for Alzheimer disease (p for trends=0.001 and 3.1x10-4, respectively), and for all dementia (p for trends=0.03 and 5.2x10-4, respectively).
Conclusion: Plasma levels of apoE are, independently of APOE genotype, associated with risk of Alzheimer disease and all dementia, but not with cerebrovascular disease. These associations were independent of cardiovascular risk factors.
- © 2013 by American Heart Association, Inc.