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

Abstract

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 β-amyloid precursor protein (AβPP) and β-amyloid (Aβ) 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 AβPP binding to tile same extent that C inhibited apoSAA binding, neither C nor PC had any effect on binding of the Aβ peptide, although antibodies to Aβ1-40 did block binding. The binding of 125I-Aβ1-40 and 125I-AβPP was inhibited by apoE3 and apoE4, but not by either apoSAA or bovine serum albumin. Bound 125I-AβPP was partially released into medium containing C, PC, apoE3, apoE4, or antibodies to AβPP. Our results indicate that AβPP but not Aβ 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 Aβ fibrils than AA fibrils.