AGGREGATION OF AMYLOID BETA-PROTEIN AS FUNCTION OF AGE AND APOLIPOPROTEIN-E IN NORMAL AND ALZHEIMERS SERUM

We compared the effect of serum from (a) 26 Alzheimer's disease (AD) p atients and 22 age-matched non-demented controls (GO) with apolipoprot ein 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 agg regation of synthetic amyloid beta-protein (AP) 1-40 by Thioflavin T f luorescence 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 bet a aggregation=0.73). However, no difference in A beta aggregation was observed in the presence of serum from AD patients and non-demented co ntrols. There was a positive correlation between serum apo E concentra tions and A beta aggregation, while there was no significant differenc e between different apo E phenotypes. The correlation coefficient in t he 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. Th ese results suggest that the apo E4 allele alone may not be responsibl e 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 correl ate with A beta aggregation. We propose that the age of an individual may be an important factor in determining the degree of A beta aggrega tion/fibrillization, and that mechanism of sequestration of A beta in serum may not be defective in AD. (C) 1998 Elsevier Science B.V.