CFM studies of A beta peptide interactions with cell membrane: a platform to monitor peptide effects

Alzheimer’s disease (AD) is an irreversible neurodegenerative pathology that induces memory dysfunctions and progressive impairment in cognitive processes and behavior. Due to the continuous increase in life expectancy, the development of new approaches to the diagnosis and treatment of AD represents a fundamental challenge for public health. The overproduction and the abnormal self-aggregation of beta- amyloid (Aβ) peptides are considered the main factors leading to the AD pathogenic cascade1. The aggregation pathway starts from Aβ monomers and proceeds to the formation of oligomers, protofibrils and finally fibrils possessing a β-sheet conformation2. The soluble oligomers are known to produce the main neurotoxic effects3; however, even preformed amyloid fibrils are able to induce cellular toxicity4. In this study confocal fluorescence microscopy (CFM) was used to monitor the effects of the interaction between Aβ peptide and cell membrane. Thanks to a fluorescent viscosity probe5, the variations of cell membrane properties in presence of Aβ were followed down to nanomolar concentrations of peptide. By means of fluorescence spectroscopy the aggregation features of Aβ peptide in the presence and in the absence of potential anti-aggregation compounds were also investigated.