AMYLOID BETA-PEPTIDE IS TRANSPORTED ON LIPOPROTEINS AND ALBUMIN IN HUMAN PLASMA

The amyloid beta-peptide (A beta) is the major constituent of neuritic plaques in Alzheimer's disease and occurs as a soluble 40-42-residue peptide in cerebrospinal fluid and blood of both normal and AD subject s. It is unclear whether A beta, once it is secreted by cells, remains free in biological fluids or is associated with other proteins and th us transported and metabolized with them. Such knowledge of the normal fate of A beta is a prerequisite for understanding the changes that m ay lead to the pathological aggregation of soluble A beta in vivo, the possible influence of certain extracellular proteins, particularly ap olipoprotein E, on plaque formation, and the pharmacology of putative A beta-lowering drugs. To address the question of A beta distribution in human biological fluids, we incubated fresh human plasma from 38 su bjects with physiological concentrations (0.5-0.7 nM) of radioiodinate d A beta(1-40) and seven plasma samples with A beta(1-42). Lipoprotein s and lipid-free proteins were separated and analyzed for bound iodina ted A beta(1-40). We found that up to 5% of A beta added to plasma is bound to selected lipoproteins: very low density, low density, and hig h density, but not lipoprotein(a). The large majority (approximate to 89%), however, is bound to albumin, and very little A beta is free. A beta distribution in plasma was not significantly influenced by apolip oprotein E genotype. We conclude that A beta is normally bound to and transported by albumin and specific lipoproteins in human plasma under physiological conditions.