High density lipoprotein inhibits assembly of amyloid beta-peptides into fibrils

The extracellular deposition of amyloid beta (A beta) in senile plaques con stitutes one of the defining hallmarks of Alzheimer's disease. A beta pepti des can aggregate spontaneously to highly insoluble amyloid fibrils, but se veral, components are likely to influence the kinetics of fibrillogenesis i n vivo. We report here that high density lipoprotein (HDL), the predominant lipoprotein in the human brain, reduces amyloid formation in vitro as dete rmined by thioflavin T fluorescence and high speed sedimentation assays. Th e inhibition occurred in a dose dependent manner, and with concentrations o f HDL above 1% resulting in more than 70% inhibition. We also examined the combined effect of apolipoprotein E (apoE) and HDL on A beta fibrillogenesi s. We found that HDL particles enriched with any of the three apoE isoforms inhibited A beta fibrillogenesis as their native counterparts. Taken toget her, these findings suggest that HDL-like particles in the brain may precen t the formation of A beta fibrils. (C) 2000 Academic Press.