Abstract
Interactions between amyloid-β peptide (Aβ) 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 Aβ. However, it is unclear whether both mechanisms lead to cytotoxicity. Thus, we aimed to analyze these two mechanisms of Aβ42 interaction with cell membranes under different Aβ aggregation states. To this end, model membrane experiments were conducted. Quantitative analysis of Aβ42 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-Aβ42 monomers or oligomers by neuro-2a cells. We found that the binding capacity of Aβ42 to membrane lipids was weak and that the amount of Aβ42 bound to membrane lipids was low. Moreover, clathrin-mediated endocytosis of Aβ42 oligomers by neuro-2a cells was observed. Endocytosis serves as a key mode of interaction between extracellular Aβ42 and neurons. These findings provide insights into the mechanisms underlying Aβ oligomer metabolism.