Endocytosis Is a Key Mode of Interaction between Extracellular β-Amyloid and the Cell Membrane.

Interactions between amyloid-beta peptide (A beta) and the cell membrane include interaction with membrane lipids and binding to membrane receptors, both of which are considered to be the toxicity mechanisms of A beta. However, it is unclear whether both mechanisms lead to cytotoxicity. Thus, we aimed to analyze these two mechanisms of A beta 42 interaction with cell membranes under different A beta aggregation states. To this end, model membrane experiments were conducted. Quantitative analysis of A beta 42 monomers or oligomers bound to the membrane of neuro-2a cells was also performed, and laser confocal microscopy was employed to assess endocytosis of FITC-A beta 42 monomers or oligomers by neuro-2a cells. We found that the binding capacity of A beta 42 to membrane lipids was weak and that the amount of A beta 42 bound to membrane lipids was low. Moreover, clathrin-mediated endocytosis of A beta 42 oligomers by neuro-2a cells was observed. Endocytosis serves as a key mode of interaction between extracellular A beta 42 and neurons. These findings provide insights into the mechanisms underlying A beta oligomer metabolism.