title: Single molecule experiments emphasize GM1 as a key player of the different cytotoxicity of structurally distinct Aβ1-42 oligomers.
abstract: It is well established that cytotoxic Aβ oligomers are the key factor that triggers the initial tissue and cell modifications eventually culminating in the development of Alzheimer's disease. Aβ1-42 oligomers display a high degree of polymorphism, and several structurally different oligomers have been described. Amongst them, two types, recently classified as A+ and A-, have been shown to possess similar size but distinct toxic properties, as a consequence of their biophysical and structural differences. Here, we have investigated by means of single molecule tracking the oligomer mobility on the plasma membrane of living neuroblastoma cells and the interaction with the ganglioside GM1, a component of membrane rafts. We have found that A+ and A- oligomers display a similar lateral diffusion on the plasma membrane of living cells. However, only the toxic A+ oligomers appear to interact and alter the mobility of GM1. We have also studied the lateral diffusion of each kind of oligomers in cells depleted or enriched in GM1. We found that the content of GM1 influences the diffusion of both types of oligomer, although the effect of the increased levels of GM1 is higher for the A+ type. Interestingly, the content of GM1 also affects significantly the mobility of GM1 molecules themselves.
authors.affiliation: European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, 50019 Florence, Italy; National Institute of Optics, National Research Council of Italy (CNR), Largo Fermi 6, 50125, Florence, Italy. Electronic address: calamai@lens.unifi.it.
authors.forename: Martino
authors.initials: M
authors.lastname: Calamai
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Clinche "Mario Serio", Università degli Studi di Firenze, 50134 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Evangelisti
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Clinche "Mario Serio", Università degli Studi di Firenze, 50134 Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cascella
authors.affiliation: European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, 50019 Florence, Italy.
authors.forename: Niccoló
authors.initials: N
authors.lastname: Parenti
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Clinche "Mario Serio", Università degli Studi di Firenze, 50134 Florence, Italy; Centro Interuniversitario per lo Studio delle Malattie Neurodegenerative (CIMN), 50134 Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Clinche "Mario Serio", Università degli Studi di Firenze, 50134 Florence, Italy; Centro Interuniversitario per lo Studio delle Malattie Neurodegenerative (CIMN), 50134 Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
authors.affiliation: European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, 50019 Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pavone
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005677:G(M1) Ganglioside
keywords: Alzheimer's disease; Aβ oligomers; GM1 ganglioside; Single molecule tracking