We compared the effect of serum from (a) 26 Alzheimer's disease (AD) patients and 22 age-matched non-demented controls (CO) with apolipoprotein E 4/4, 3/3 or 3/2 phenotypes, and (b) 17 normal young (aged 15-41 years) and 21 normal elderly (aged 64-83 years) people on in vitro aggregation of synthetic amyloid beta-protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. A beta 1-40 aggregation in presence of serum from the normal elderly group was significantly higher as compared to the normal young group (correlation coefficient between age and A beta aggregation=0.73). However, no difference in A beta aggregation was observed in the presence of serum from AD patients and non-demented controls. There was a positive correlation between serum apo E concentrations and A beta aggregation, while there was no significant difference between different apo E phenotypes. The correlation coefficient in the AD 4/4 (0.65) was higher than the CO 4/4 group (0.04), while it was lower in the AD 3/3 group (-0.12) than in the CO 3/3 (0.39) group. These results suggest that the apo E4 allele alone may not be responsible for A beta fibril formation in AD; other factors may be involved in increasing risk for AD pathogenesis in those having the apo E4 allele. The severity of dementia and serum albumin levels also did not correlate with A beta aggregation. We propose that the age of an individual may be an important factor in determining the degree of A beta aggregation/fibrillization, and that mechanism of sequestration of A beta in serum may not be defective in AD.