Apolipoprotein E Polymorphism and Silent Microangiopathy-Related Cerebral Damage

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Abstract
Background and Purpose Microangiopathy-related cerebral damage (MARCD) includes white matter abnormalities and lacunar infarctions and represents a common MRI observation in subjects above 50 years of age. The risk factors of such brain abnormalities are not fully determined. The goal of this study was to determine whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the occurrence of MARCD. Methods Brain MRI (1.5 T) was performed in 280 individuals (ages 50 to 75 years) without neuropsychiatric disease randomly selected from the official register of residents of the city of Graz, Austria. All study participants underwent apoE genotyping, carotid Doppler sonography, electrocardiography, echocardiography, and a complete blood chemistry panel. MARCD was defined as evidence of early confluent and confluent white matter hyperintensities or lacunes. Carotid atherosclerosis was graded on a five-point scale ranging from not present (0) to complete occlusion (5). Results MARCD occurred in 61 individuals (21%). The distribution of apoE genotypes differed significantly between subjects with and without MARCD ( P =.036). Subjects with such findings more commonly had the ε2/ε3 genotype (24.6% versus 10%) at similar frequencies of genotypes containing the ε4 allele. The ε2/ε3 genotype was associated with lower levels of total cholesterol ( P =.0009), LDL cholesterol ( P =.00001), and apolipoprotein B ( P =.00001). Also, there was a nonsignificant trend toward less cardiac disease. Other major vascular risk factors and carotid abnormalities were similar among the various genotypes. Multiple logistic regression analysis created a model of significant MARCD predictors, including age (odds ratio [OR], 1.1 per year), hypertension (OR, 3.4), and the apoE ε2/ε3 genotype (OR, 3.0). Conclusions These data suggest an association between the apoE ε2/ε3 genotype and MARCD despite favorable effects on the lipid profile and cardiac disease.