O2-13-05: The effects of ApoE genotype and serum plasmalogen metabotype on cognition and the odds of Alzheimer's disease in older persons

Presence of the Apolipoprotein E (ApoE) ε4 allele or low serum ethanolamine plasmalogen (PlsEtn) levels have been shown to be associated with Alzheimer's disease (AD) and decreased cognition.We investigated potential interactions between ApoE genotype and serum PlsEtn levels on cognition and AD. Using a community-based sample of 1196 well characterized elderly persons from the Rush University Religious Orders Study and Memory and Aging Project, the relationships between ApoE genotype, PlsEtn biosynthesis, cognition and AD diagnosis were investigated. A quantitative PlsEtn Biosynthesis Value (PBV) was generated for each person by combining the relative serum levels of three key PlsEtn species. Subjects were classified into one of three genotypes (ε2=ε2ε3, ε3=ε3ε3, ε4=ε3ε4+ε4ε4) and one of three metabotypes (Pls1=81-100th; Pls2=21-80th; Pls3=0-20th PBV percentiles). Higher PBV was associated with higher cognition (coef=0.66, p<0.001). Relative to ε3, ε2 was associated with higher (coef=0.19, p<0.001) and ε4 with lower (coef=-0.23, p<0.001) cognition. Relative to persons in ε3:Pls2, the odds of AD were higher for both low PBV (ε3:Pls3: OR=3.3 (95%CI 1.9-5.8), p<0.001)and ε4 (ε4:Pls2: OR=2.5 (95%CI 1.4-4.5), p=0.002); the odds of AD were lower in ε2 (ε2:Pls1-3: OR=0.18 (95%CI 0.04-0.78), p<0.05) and Pls1 (ε3:Pls1: OR=0.29 (95%CI 0.08-1.0), p<0.05). Relative to persons in ε3:Pls2, the odds of AD was increased in ε4:Pls3: OR=5.7 (95%CI 2.7-11.9), p<0.001) but not increased in ε4:Pls1 subjects. The Pls3 metabotype and ε4 genotype were observed to be independently associated with an increases odds of AD. The ApoE ε4 genotype did not result in an increased odds of AD in subjects wth a Pls1 metabotype. The odds of AD associated with ApoE genotype is dependent upon the underlying PlsEtn metabotype.