The Fibril Forming Region of the β-Amyloid Precursor Differs from That of the Amyloid A Precursor in Its Interaction with Lipids1

Lipid Binding to Amyloid β‐Peptide Aggregates: Preferential Binding of Cholesterol as Compared with Phosphatidylcholine and Fatty Acids

“…We did not observe lipid binding to Aß1 ..40 where polymers were not detected (0, 1, or 3 h of incubation). The absence of lipid binding to Aß140 that had been preincubated for~3 h in the present study is similar to an earlier study that reported that cholesterol and PC did not bind to Aß1..40 that had been incubated with the lipids for 3 h (Liang et al, 1996). The earliest that we observed a significant increase in fluorescence intensity of labeled lipids was after Aß1..40 had been incubated for 6 h, which was accompanied by appearance of peptide polymers.…”

“…The finding that cholesterol preferentially binds to aggregated Aß is further support for the association between cholesterol and Alzheimer' s disease (Mason et al, 1992;Schmechel et al, 1993;Hartmann et al, 1994;Poirier, 1994;Bodovitz and Klein, 1996;Liang et al, 1996). The apoE genotype is associated with Alzheimer's disease (Schmechel et al, 1993;Poirier et al, 1993;Poirier, 1994).…”

“…Aß may bind cholesterol and possibly other lipids. However, it was recently reported that cholesterol and PC did not bind to Aß but that those lipids did bind to the Aß precursor protein (Liang et al, 1996). In that study, Aß was incubated with cholesterol or PC for 3 h. It is possible that lipid binding to Aß is dependent on peptide aggregation.…”

“…Aß (10_6 M) in 1 ml of distilled water was incubated for 0,1,3,6,21, and 24 h in darkness with continuous stirring at 37°C.Aggregates of Aß1_40 formed during incubation were separated with 11% nonreducing SDS-PAGE procedures as previously described (Burdick et al, 1992). A set of proteins containing aprotinin, a-lactalbumin, bovine trypsin inhibitor, glyceraldehyde-3-phosphate dehydrogenase, and ovalbuminum were used as reference standards.…”

“…Lipid binding was determined using fluorescentlabeled lipids. Incubation of Aß140 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 Aß140 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 Aß140 that had been incubated for 6, 21, and 24 h in which Aß140 polymers were detected.…”