Interaction of amyloid precursor protein and beta-secretase on the cell surface

Accumulation of amyloid-beta-peptide (Abeta) in senile plaques is a characteristic feature for Alzheimer's disease. The amyloid precursor protein (APP) is cleaved sequentially by beta-site APP-cleaving enzyme (BACE) and gamma-secretase to release Abeta. Recent data indicate that production, clearance, and aggregation of Aß are highly dependent on the specific neuronal subcellular localization wherein Aß is generated. We tested the hypothesis that APP and BACE are co-localized within lipid domains (e.g. lipid rafts) on the cell surface. We used Total internal reflection fluorescence microscopy (TIRFM) combined wi…