Abstract
One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the production of Aβ. Moreover, APOE is the main cholesterol carrier in the brain, and it has been reported as a risk factor for this disease. This study evaluates the relationship between ACAT1 and APOE genetic variants with susceptibility for the development of Alzheimer's disease and other dementias. We examined four ACAT1 polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in the APOE gene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR = 0.34, 95% CI = 0.23-0.46; p < 0.001) and one risk haplotype: CGGA (OR = 1.87, 95% CI = 1.34-2.60; p < 0.001) for the development of dementia. Subjects identified as APOE-ε4 allele carriers had a higher risk of developing dementia compared with non-carriers, OR = 13.33 (95% CI = 3.14-56.31). The results support the hypothesis that the ACAT1 gene, together with the APOE gene, plays an important role in susceptibility to the development of dementia and shows genetic characteristics of the Mexican population that can be used to identify the population at risk.
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