The fibril forming region of the beta-amyloid precursor differs from that of the amyloid A precursor in its interaction with lipids

Since the amyloid A (AA) precursor, serum amyloid A (apoSAA), has been shown to bind cholesterol (C) in the AA fibril forming region, we investigated the interaction of the beta-amyloid precursor protein (A beta PP) and beta-amyloid (A beta) peptide with C and phosphatidyl choline (PC) by measuring changes in binding to microtiter wells at physiological pH and ionic strength. While either C or PC inhibited A beta PP binding to the same extent that C inhibited apoSAA binding, neither C nor PC had any effect on binding of the A beta peptide, although antibodies to A beta 1-40 did block binding. The binding of I-125-A beta 1-40 and 125I-A beta PP was inhibited by apoE3 and apoE4, but not by either apoSAA or bovine serum albumin. Bound I-125-A beta PP was partially released into medium containing C, PC, apoE3, apoE4, or antibodies to A beta PP. Our results indicate that A beta PP but not A beta peptide can be retained in solution in the presence of C and PC and suggest that this failure to interact with lipids may account for the greater insolubility of A beta fibrils than AA Fibrils. (C) 1996 Academic Press, Inc.