title: Molecular architecture of Aβ fibrils grown in cerebrospinal fluid solution and in a cell culture model of Aβ plaque formation.
abstract: OBJECTIVE
  The detailed structure of brain-derived Aβ amyloid fibrils is unknown. To approach this issue, we investigate the molecular architecture of Aβ(1-40) fibrils grown in either human cerebrospinal fluid solution, in chemically simple phosphate buffer in vitro or extracted from a cell culture model of Aβ amyloid plaque formation.
  
  
  METHODS
  We have used hydrogen-deuterium exchange (HX) combined with nuclear magnetic resonance, transmission electron microscopy, seeding experiments both in vitro and in cell culture as well as several other spectroscopic measurements to compare the morphology and residue-specific conformation of these different Aβ fibrils.
  
  
  CONCLUSIONS
  Our data reveal that, despite considerable variations in morphology, the spectroscopic properties and the pattern of slowly exchanging backbone amides are closely similar in the fibrils investigated. This finding implies that a fundamentally conserved molecular architecture of Aβ peptide fold is common to Aβ fibrils.
authors.affiliation: a School of Medicine, Deakin University , East Geelong , VIC , Australia .
authors.forename: Megan
authors.initials: M
authors.lastname: Garvey
authors.affiliation: b Institute for Physics, Biophysics, Martin-Luther-University Halle-Wittenberg , Halle (Saale) , Germany .
authors.forename: Monika
authors.initials: M
authors.lastname: Baumann
authors.affiliation: c Institute for Pharmaceutical Biotechnology, Ulm University , Ulm , Germany .
authors.forename: Melanie
authors.initials: M
authors.lastname: Wulff
authors.affiliation: c Institute for Pharmaceutical Biotechnology, Ulm University , Ulm , Germany .
authors.forename: Senthil T
authors.initials: ST
authors.lastname: Kumar
authors.affiliation: c Institute for Pharmaceutical Biotechnology, Ulm University , Ulm , Germany .
authors.forename: Daniel
authors.initials: D
authors.lastname: Markx
authors.affiliation: d Boston University School of Medicine , Boston , MA , USA .
authors.forename: Isabel
authors.initials: I
authors.lastname: Morgado
authors.affiliation: e Leibniz-Institute for Infection Biology and Natural Product Research, Hans-Knöll-Institut (HKI) , Jena , Germany , and.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knüpfer
authors.affiliation: e Leibniz-Institute for Infection Biology and Natural Product Research, Hans-Knöll-Institut (HKI) , Jena , Germany , and.
authors.forename: Uwe
authors.initials: U
authors.lastname: Horn
authors.affiliation: f Institute for Neuropathology, Otto-von-Guericke University , Magdeburg , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: c Institute for Pharmaceutical Biotechnology, Ulm University , Ulm , Germany .
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
authors.affiliation: b Institute for Physics, Biophysics, Martin-Luther-University Halle-Wittenberg , Halle (Saale) , Germany .
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
mesh_terms: D000682:Amyloid / Q000134:cerebrospinal fluid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000737:chemistry*; D002021:Buffers; D002460:Cell Line; D017124:Conserved Sequence; D041961:Deuterium Exchange Measurement; D006801:Humans; D008954:Models, Biological; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000737:chemistry*; D010710:Phosphates / Q000134:cerebrospinal fluid / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D012996:Solutions
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D002021:Buffers; D010446:Peptide Fragments; D010710:Phosphates; D012996:Solutions; C078592:amyloid beta-protein (1-40)
keywords: Alzheimer’s disease; H/D-exchange; NMR; amyloid fibrils; neurodegeneration