Abstract
Using a community sample of 1205 elderly persons, we investigated the associations and potential interactions between Apolipoprotein E (APOE) genotype and serum phosphatidylethanolamine (PlsEtn) on cognition and dementia. For each person, APOE genotype, PlsEtn Biosynthesis value (PBV, the combination of three key PlsEtn species), cognition (the combination of five specific cognitive domains), and diagnosis of dementia was determined. APOE genotype and PBV were observed to be non-interacting (p > 0.05) and independently associated with cognition: APOE (relative to ε3ε3:ε2ε3 (Coef = 0.14, p = 4.2 × 10−2); ε3ε4/ε4ε4 (Coef = −0.22, p = 6.2 × 10−5); PBV (Coef = 0.12, p = 1.7 × 10−7) and dementia: APOE (relative to ε3ε3:ε2ε3 (Odds Ratio OR = 0.44, p = 3.0 × 10−2); ε3ε4/ε4ε4 (OR = 2.1, p = 2.2 × 10−4)); PBV (OR = 0.61, p = 3.3 × 10−6). Associations are expressed per standard deviation (SD) and adjusted for serum lipids and demographics. Due to the independent and non-interacting nature of the APOE and PBV associations, the prevalence of dementia in APOE ε3ε4/ε4ε4 persons with high PBV values (>1 SD from mean) was observed to be the same as APOE ε3ε3 persons (14.3% versus 14.0%). Similarly, the prevalence of dementia in APOE ε3ε3 persons with high PBV values was only 5.7% versus 6.7% for APOE ε2ε3 persons. The results of these analyses indicate that the net effect of APOE genotype on cognition and the prevalence of dementia is dependent upon the plasmalogen status of the person.
Highlights
Apolipoprotein E (APOE) is the predominant lipoprotein in the brain [1] and is the strongest genetic risk factor for Alzheimer’s disease (AD) [2]
The results of these analyses indicate that the net effect of APOE genotype on cognition and the prevalence of dementia is dependent upon the plasmalogen status of the person
We investigated the associations between APOE genotype, serum plasmalogen ethanolamine (PlsEtn) levels, and serum lipids, such as HDL, on cognition and odds of AD in a well-characterized community-based group of 1205 elderly persons enrolled in the Religious Orders Study (ROS) [27] or Rush Memory and
Summary
Apolipoprotein E (APOE) is the predominant lipoprotein in the brain [1] and is the strongest genetic risk factor for Alzheimer’s disease (AD) [2]. Ε2) [24,25]; and differential binding affinities of the APOE isoforms to the low-density lipoprotein receptor (LDLR) simultaneously affect cortical cholesterol levels and cognitive function [26] Both PlsEtn [23] and ApoE [20] seem to play a role in cholesterol homeostasis and efflux, which could be potential mechanisms by which these variables affect AD pathogenesis. If membrane cholesterol changes and cognition are downstream effects of AD pathology, no interaction should be observed To test this hypothesis, we investigated the associations between APOE genotype, serum PlsEtn levels, and serum lipids, such as HDL, on cognition and odds of AD in a well-characterized community-based group of 1205 elderly persons enrolled in the Religious Orders Study (ROS) [27] or Rush Memory and. Aging Project (MAP) [28]
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