• Amyloid β-peptide;
  • Cholesterol;
  • Phosphatidylcholine;
  • Fatty acids;
  • Alzheimer's disease


  1. Top of page
  2. Abstract

Abstract: Amyloid β-peptide (Aβ) aggregates are one of the key neuropathological characteristics of Alzheimer's disease. Aβ belongs to a group of proteins that aggregate and form β-sheets, and some of these proteins bind cholesterol and other lipids. The purpose of the experiments reported here was to determine if cholesterol, fatty acids, and phosphatidylcholine (PC) would bind to Aβ1–40 and if such binding would be dependent on aggregation of Aβ1–40. Lipid binding was determined using fluorescent-labeled lipids. Incubation of Aβ1–40 for 0, 1, 3, 6, 21, and 24 h resulted in aggregation of the peptide with formation of dimers, trimers (1–24 h), and polymers (6–24 h) as determined by sodium dodecyl sulfate-gel electrophoresis. No change in the fluorescence of the lipids was observed when lipids were added to Aβ1–40 that had been incubated for 0, 1, or 3 h. However, the fluorescence intensities of cholesterol, saturated fatty acids, and PC were significantly increased (p < 0.0001) when added to Aβ1–40 that had been incubated for 6, 21, and 24 h in which Aβ1–40 polymers were detected. The binding affinity of cholesterol to Aβ1–40 polymers (KD of 3.24 ± 0.315 × 10−9M) was markedly higher as compared with the other lipids (stearic acid, 9.42 ± 0.41 × 10−8M; PC, 7.07 ± 0.12 × 10−7M). The results of this study indicate that Aβ1–40 polymers bind lipids and have a higher affinity for cholesterol than PC or saturated fatty acids. Aggregated Aβ1–40 may affect lipid transport between cells or remove specific lipids from membranes, and such effects could contribute to neuronal dysfunction.

Abbreviations used: Aβ, amyloid β-peptide; apoE, apolipoprotein E; CMC, critical micelle concentration; NBD, 7-nitrobenz-2-oxa-1,3-diazol-4-yl; NBD-cholesterol, 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-23,24-bisnor-5-cholen-3β-ol; NBD-PC, 2-[12-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]dodecanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine; NBD-stearic acid, 12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]octadecanoic acid; PBS, phosphate-buffered-saline; PC, phosphatidylcholine; pyrene, benzo[def]phenanthrene; pyrenecholesterol, 1-pyrenemethyl 3β-hydroxy-22,23-bisnor-5-cholenate; pyrene-PC, 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine; pyrenehexadecanoic acid, 1-pyrenehexadecanoic acid; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.