Plasma levels of apolipoprotein E and risk of dementia in the general population

OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis. METHODS: Using 75,708 participants from the general population, we tested whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype. RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia increased from the highest to the lowest apoE tertile (p for trends T GT promoter genotype, associated with low plasma apoE levels, remained significantly associated with increased risk of Alzheimer disease after adjustment for ε2/ε3/ε4 APOE genotype (HR = 1.56, 95% CI = 1.05-2.30). INTERPRETATION: Low plasma levels of apoE are associated with increased risk of future Alzheimer disease and all dementia in the general population, independent of ε2/ε3/ε4 APOE genotype. This is clinically relevant, because no plasma biomarkers are currently implemented. Hence, plasma levels of apoE may be a new, easily accessible preclinical biomarker.