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) precursoir, 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 (AbetaPP) and beta-amyloid (Abeta) 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 AbetaPP binding to the same extent that C inhibited apoSAA binding, neither C nor PC had any effect on binding of the Abeta peptide, although antibodies to Abeta1-40 did block binding. The binding of (125)I-Abeta1-40 and (125)I-AbetaPP was inhibited by apoE3 and apoE4, but not by either apoSAA or bovine serum albumin. Bound (125)I-AbetaPP was partially released into medium containing C, PC, apoE3, apoE4, or antibodies to AbetaPP. Our results indicate that AbetaPP but not Abeta 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 Abeta fibrils than AA fibrils.
Liang
J S
JS
Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.
Fine
R E
RE
Abraham
C R
CR
Sipe
J D
JD
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D001053:Apolipoproteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D010713:Phosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D016564:Amyloid beta-Protein Precursor; D001053:Apolipoproteins; D007457:Iodine Radioisotopes; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D002784:Cholesterol