title: Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: a force spectroscopy study on living hippocampal neurons.
abstract: Small soluble species of amyloid-beta (Aβ) formed during early peptide aggregation stages are responsible for several neurotoxic mechanisms relevant to the pathology of Alzheimer's disease (AD), although their interaction with the neuronal membrane is not completely understood. This study quantifies the changes in the neuronal membrane elasticity induced by treatment with the two most common Aβ isoforms found in AD brains: Aβ40 and Aβ42. Using quantitative atomic force microscopy (AFM), we measured for the first time the static elastic modulus of living primary hippocampal neurons treated with pre-aggregated Aβ40 and Aβ42 soluble species. Our AFM results demonstrate changes in the elasticity of young, mature and aged neurons treated for a short time with the two Aβ species pre-aggregated for 2 hours. Neurons aging under stress conditions, showing aging hallmarks, are the most susceptible to amyloid binding and show the largest decrease in membrane stiffness upon Aβ treatment. Membrane stiffness defines the way in which cells respond to mechanical forces in their environment and has been shown to be important for processes such as gene expression, ion-channel gating and neurotransmitter vesicle transport. Thus, one can expect that changes in neuronal membrane elasticity might directly induce functional changes related to neurodegeneration.
authors.affiliation: Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001, Leuven, Belgium.|imec, Kapeldreef 75, B-3001 Leuven, Belgium.
authors.forename: Andreea-Alexandra
authors.initials: AA
authors.lastname: Ungureanu
authors.affiliation: VIB Center for the Biology of Diseases, ON 4 Campus Gasthuisberg, Herestraat 49, B-3001, Leuven, Belgium.
authors.forename: Iryna
authors.initials: I
authors.lastname: Benilova
authors.affiliation: imec, Kapeldreef 75, B-3001 Leuven, Belgium.
authors.forename: Olga
authors.initials: O
authors.lastname: Krylychkina
authors.affiliation: imec, Kapeldreef 75, B-3001 Leuven, Belgium.
authors.forename: Dries
authors.initials: D
authors.lastname: Braeken
authors.affiliation: VIB Center for the Biology of Diseases, ON 4 Campus Gasthuisberg, Herestraat 49, B-3001, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
authors.affiliation: Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001, Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Van Haesendonck
authors.affiliation: VIB Center for the Biology of Diseases, ON 4 Campus Gasthuisberg, Herestraat 49, B-3001, Leuven, Belgium.|CSIC, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid Campus Cantoblanco, 28049 Madrid, Spain.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
authors.affiliation: Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001, Leuven, Belgium.|imec, Kapeldreef 75, B-3001 Leuven, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Bartic
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence; D055119:Elastic Modulus; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)