APOLIPOPROTEIN E (apoE) and the beta-amyloid peptide are both found in the senile plaques associated with Alzheimer's disease. Several studies have recently determined that apoE can prevent beta-amyloid fibril (A beta f) formation in vitro. In vivo, apoE is normally associated with a lipid source. We show that both recombinant and purified plasma apoE inhibit A beta f formation in a dose-dependent manner. The three major apoE isoforms were equipotent at inhibiting A beta f formation. ApoE associated with either cholesterol-containing liposomes or very low density lipoproteins displayed less potent inhibition of A beta f formation than their unlipidated counterparts. These results indicate that the presence of associated lipids reduce the ability of apoE to inhibit the formation of A beta f in vitro. (C) 1998 Lippincott Williams & Wilkins.