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Lipid Binding to Amyloid β‐Peptide Aggregates: Preferential Binding of Cholesterol as Compared with Phosphatidylcholine and Fatty Acids
Author(s) -
Avdulov Nicolai A.,
Chochina Svetlana V.,
Igbavboa Urule,
Warden Christopher S.,
Vassiliev Alexei V.,
Wood W. Gibson
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69041746.x
Subject(s) - chemistry , phosphatidylcholine , peptide , cholesterol , stearic acid , biochemistry , sodium dodecyl sulfate , beta (programming language) , amyloid beta , fluorescence , chromatography , phospholipid , organic chemistry , membrane , quantum mechanics , computer science , programming language , physics
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 Aβ 1–40 and if such binding would be dependent on aggregation of Aβ 1–40 . Lipid binding was determined using fluorescent‐labeled lipids. Incubation of Aβ 1–40 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 Aβ 1–40 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 Aβ 1–40 that had been incubated for 6, 21, and 24 h in which Aβ 1–40 polymers were detected. The binding affinity of cholesterol to Aβ 1–40 polymers ( K D of 3.24 ± 0.315 × 10 −9 M ) was markedly higher as compared with the other lipids (stearic acid, 9.42 ± 0.41 × 10 −8 M ; PC, 7.07 ± 0.12 × 10 −7 M ). The results of this study indicate that Aβ 1–40 polymers bind lipids and have a higher affinity for cholesterol than PC or saturated fatty acids. Aggregated Aβ 1–40 may affect lipid transport between cells or remove specific lipids from membranes, and such effects could contribute to neuronal dysfunction.