Fluorescent Analysis of the Cell-Selective Alzheimer's Disease Aβ Peptide Surface Membrane Binding: Influence of Membrane Components

We performed a fluorescent analysis of the binding of Aβ to the surface membrane of different types of cells lines such as PC12, GT1-7, and ex vivo neurons. Analyses were performed on sorted cells with membrane bound Aβ Competitive binding between Aβ phosphatidyl serine- (PtdSer-) specific binder annexin V and an anti-PtdSer antibody provided compelling data confirming the involvement of PtdSer as one of the surface membrane signal molecules for Aβ. We found that populations of cells that exhibited high surface membrane binding affinity for Aβ also show higher membrane cholesterol levels compared to cells that did not bind Aβ. This direct relationship was upheld in cholesterol-enriched or cholesterol-depleted cell membranes. We conclude that the initial process for the cell-selective binding by Aβ, to later conversion of elemental Aβ units into larger structures such as fibrils or to the potentially toxic ion channel aggregates, is highly influenced by the membrane content of PtdSer and cholesterol in the cell surface membrane.