title: Fluorimetric detection of the earliest events in amyloid β oligomerization and its inhibition by pharmacologically active liposomes.
abstract: BACKGROUND
  Amyloid β (Aβ) peptide aggregation is the main molecular mechanism underlying the development of Alzheimer's disease, the most widespread form of senile dementia worldwide. Increasing evidence suggests that the key factor leading to impaired neuronal function is accumulation of water-soluble Aβ oligomers rather than formation of the senile plaques created by the deposition of large fibrillary aggregates of Aβ. However, several questions remain about the preliminary steps and the progression of Aβ oligomerization.
  
  
  METHODS
  We show that the initial stages of the aggregation of fluorescently labeled Aβ can be determined with a high degree of precision and at physiological (i.e., nanomolar) concentrations by using either steady-state fluorimetry or time-correlated single-photon counting.
  
  
  RESULTS
  We study the dependence of the oligomerization extent and rate on the Aβ concentration. We determine the chemical binding affinity of fluorescently labeled Aβ for liposomes that have been recently shown to be pharmacologically active in vivo, reducing the Aβ burden within the brain. We also probe their capacity to hinder the Aβ oligomerization process in vitro.
  
  
  CONCLUSIONS
  We introduced a fluorescence assay allowing investigation of the earliest steps of Aβ oligomerization, the peptide involved in Alzheimer's disease. The assay proved to be sensitive even at Aβ concentrations as low as those physiologically observed in the cerebrospinal fluid.
  
  
  CONCLUSIONS
  This work represents an extensive and quantitative study on the initial events of Aβ oligomerization at physiological concentration. It may enhance our comprehension of the molecular mechanisms leading to Alzheimer's disease, thus paving the way to novel therapeutic strategies.
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy. Electronic address: luca.nardo@unimib.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Nardo
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Brioschi
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cazzaniga
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Orlando
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Minniti
authors.affiliation: Dept. of Science and High Technology, University of Insubria, Via Valleggio 11, 22100, Como (CO), Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lamperti
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Gregori
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cassina
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Doriano
authors.initials: D
authors.lastname: Brogioli
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Salerno
authors.affiliation: Dept. of Health Sciences, University of Milano Bicocca & Nanomedicine Center NanoMIB, Via Cadore 48, 20900, Monza (MB), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mantegazza
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D013050:Spectrometry, Fluorescence
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid β; Fluorimetric assay; Liposome; Oligomerization