Characterization of the interactions between β-amyloid peptide and the membranes of human SK-N-SH cells

Interaction of β-amyloid peptide (Aβ) with cell membranes is thought to be an initial step in Alzheimer's disease (AD). However, some data are controversial and the underlying mechanisms remain unclear. In this report, two populations of Aβ were found in human SK-N-SH neuroblastoma cells. Notably, one of the Aβ populations was tightly inserted into the plasma membrane whilst the other was only peripherally associated with it. Here we show that reducing membrane cholesterol decreased the number of membrane-embedded Aβs and increased the number of membrane-attached Aβs. We also found that cholesterol depletion inhibited Aβ degradation and exacerbated Aβ-mediated cytotoxicity. Our detailed and direct observations provide specific insights into the mechanism of Aβ membrane-associated toxicity.