Genetic susceptibility in Alzheimer's disease and the role of lipid metabolism.

摘要

With significant evidence supporting the role of lipid transport and/or lipid metabolism in late onset Alzheimer's Disease (LOAD) susceptibility, we hypothesized that polymorphisms in genes coding for proteins involved in lipid pathways would make good candidates in an investigation of genetic risk and LOAD. We selected six genes associated both with LOAD and either directly or indirectly with lipid pathways to test in three case-control populations: Brain-derived Neurotrophic Factor (BDNF), Transthyretin (TTR), Tumor Necrosis Factor alpha (TNFa), Low-density Lipoprotein Receptor-related Protein (LRP1), Apolipoprotein L-3 (APOL3), and Sterol O-acyltransferase 1 (SOAT1). As an additional, exploratory analysis, we tested the hypothesis that dietary intake of lipids may modify the effect of these genes. Our results demonstrate a potentially significant role of LRP1 in protection against LOAD in the younger LOAD case-control population. In the elderly LOAD case-control population, we observed an association of borderline significance for TNFa, APOL3, and BDNF. Additional results of interest include observed but statistically non-significant effect modification of TTR by dietary fish intake.