Sera obtained in the immediate postmortem from 100 individuals, 64 neuropathologically diagnosed Alzheimer's disease (AD) cases and 36 nondemented controls, were analyzed for cholesterol, lipoproteins, apolipoproteins (Apo), and triglycerides. All individuals were ApoE genotyped, and the amounts of Abeta (N-40 and N-42) in cerebral cortex of AD and control subjects were determined. When compared to controls, AD individuals had significantly higher LDL cholesterol (P = 0.006), ApoB (P = 0.018), Abeta N-40 (P = 0.024) and Abeta N-42 (P < 0.001), and significantly lower HDL cholesterol (P = 0.040). There were positive correlations between the levels of serum total cholesterol (r = 0.359, P = 0.004), LDL cholesterol (r = 0.328, P = 0.008), and ApoB (r = 0.395, P = 0.001) to the amount of Abeta N-42 in AD brains, but not to Abeta N-40. These correlations were independent of ApoE genotype and were not seen in the control group. The present results suggest for the first time that elevated serum cholesterol, especially in the form of LDL, influences the expression of AD-related pathology.