title: Real-time and single fibril observation of the formation of amyloid beta spherulitic structures.
abstract: In Alzheimer disease, amyloid beta, a 39-43-residue peptide produced by cleavage from a large amyloid precursor protein, undergoes conformational change to form amyloid fibrils and deposits as senile amyloid plaques in the extracellular cerebral cortices of the brain. However, the mechanism of how the intrinsically linear amyloid fibrils form spherical senile plaques is unknown. With total internal reflection fluorescence microscopy combined with the use of thioflavin T, an amyloid-specific fluorescence dye, we succeeded in observing the formation of the senile plaque-like spherulitic structures with diameters of around 15 microm on the chemically modified quartz surface. Real-time observation at a single fibrillar level revealed that, in the absence of tight contact with the surface, the cooperative and radial growth of amyloid fibrils from the core leads to a huge spherulitic structure. The results suggest the underlying physicochemical mechanism of senile plaque formation, essential for obtaining insight into prevention of Alzheimer disease.
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tadato
authors.initials: T
authors.lastname: Ban
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morigaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yuba
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D011487:Protein Conformation; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides