Plasma levels of apolipoprotein E and risk of dementia in the general population.
Level 3 - non-randomized controlled study
Prospective cohort study of general population participants
PubMed 25469919 · doi:10.1002/ana.24326
What was done
In a prospective general population cohort of 75,708 participants, investigators tested whether baseline plasma levels of apolipoprotein E (apoE) were associated with incident Alzheimer disease and all-cause dementia, and evaluated if the relationship was independent of APOE ε2/ε3/ε4 genotype and the -219G>T promoter polymorphism.
What was found
Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all-cause dementia increased across descending apoE tertiles (p for trend < 1 × 10^-6). Comparing the lowest to the highest tertile, adjusted HRs were 2.68 (95% CI 2.04–3.52) for Alzheimer disease and 1.80 (95% CI 1.52–2.13) for all dementia. Following further adjustment for APOE ε2/ε3/ε4 genotype, the trend remained significant for Alzheimer disease (p = 0.007) and all dementia (p = 0.04), with no evidence of interaction between plasma apoE tertiles and APOE genotype (p = 0.53 and p = 0.79, respectively). Additionally, the -219G>T GT promoter genotype was associated with increased Alzheimer disease risk after adjusting for APOE genotype (HR 1.56, 95% CI 1.05–2.30).
Why it matters
Plasma apoE level acts as an accessible preclinical biomarker that predicts dementia risk independently of standard APOE ε4 genetic status.
Limits
The abstract does not report duration of follow-up, participant demographics, specific assay methods, or absolute event numbers. Observational design leaves potential for residual confounding, and circulating peripheral apoE levels may not directly reflect central nervous system apoE metabolism.
Cited by
- context Serum levels of APOE are more predictive of Alzheimer's disease risk than APOE genotype.