Gene dose effect of the APOE-epsilon4 allele on plasma HDL cholesterol level in patients with Alzheimer's disease.

It has been reported that decreased serum high density lipoprotein (HDL) cholesterol level is related with severity of Alzheimer's disease (AD). Here, 82 patients with AD and 40 non-demented individuals were examined to determine how the APOE-epsilon4 allele modifies plasma cholesterol fractions. In adjusting for age, sex and plasma albumin level, plasma HDL cholesterol level was inversely correlated with the APOE-epsilon4 dose only in the patients (P = 0.0048), while plasma low density lipoprotein (LDL) cholesterol level tended to be correlated with the APOE-epsilon4 dose in both groups, although this was not significant. The ratio of LDL to HDL cholesterol in the patients showed a similar correlation with the APOE-epsilon4 dose to that in the controls, and this correlation was evident (P = 0.0069) after putting all subjects into one group. However, neither HDL nor LDL cholesterol levels showed significant differences between the groups. These results indicated that the APOE-epsilon4 dose affects the composition of plasma cholesterol, and suggested that the genetic effect on plasma lipid metabolism could be distinctive in patients with AD.