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

Katrine Laura Rasmussen1,2,*, Anne Tybjærg-Hansen1,2, Børge G Nordestgaard2,3, Ruth Frikke-Schmidt1,2

1Department of Clinical Biochemistry, Rigshospitalet, 2Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 3Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark

Introduction: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia.

Objectives: It remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis.

Methods: Using 76,386 participants from the general population, we tested whether low plasma levels of apoE at study enrollment predicted increased risk of future Alzheimer disease and all dementia, and whether this association was independent of 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: 4×10-13 and 1×10-11). Multifactorially adjusted HRs for lowest versus highest tertile were 2.75 (2.08-3.62) and 1.79 (1.51-2.13) for Alzheimer disease and all dementia, respectively. After further adjustment for APOE genotype, plasma apoE tertiles remained associated with Alzheimer disease (p for trend=0.006) and all dementia (p for trend=0.05). Also, in ε32+ε33 and ε43+ε44 individuals separately, multifactorially adjusted HRs increased from the highest to the lowest apoE tertile for Alzheimer disease (p for trends=0.001 and 3×10-4, respectively), and for all dementia (p for trends=0.03 and 5×10-4, respectively). Plasma apoE tertiles did not interact with APOE genotype in predicting Alzheimer disease (p=0.55) or all dementia (p=0.57).

Conclusion: Low plasma levels of apoE are associated with increased risk of future Alzheimer disease and all dementia in the general population, independent of APOE genotype. This is clinically relevant, because no plasma biomarkers currently are implemented. Hence, plasma levels of apoE may be a new, easily accessible preclinical biomarker.

Keywords: Biomarker, Brain