title: QIAD assay for quantitating a compound's efficacy in elimination of toxic Aβ oligomers.
abstract: Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer's disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAβ3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aβ aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease.
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Brener
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Dunkelmann
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Gremer
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Mirecka
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Inga
authors.initials: I
authors.lastname: Kadish
authors.affiliation: Institute of Neuroscience and Medicine (INM-4), Research Centre Jülich (FZJ), 52425 Jülich, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Willuweit
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Kutzsche
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Jürgens
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rudolph
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tusche
authors.affiliation: Institute for Bioorganic Chemistry, Heinrich-Heine-Universität Düsseldorf, 52426 Jülich, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bongen
authors.affiliation: Institute for Bioorganic Chemistry, Heinrich-Heine-Universität Düsseldorf, 52426 Jülich, Germany.|Institut für Bio- und Geowissenschaften: Biotechnologie (IBG-1), Forschungszentrum Jülich, 52428 Jülich, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Pietruszka
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Filipp
authors.initials: F
authors.lastname: Oesterhelt
authors.affiliation: Institute of Neuroscience and Medicine (INM-4), Research Centre Jülich (FZJ), 52425 Jülich, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Dep. Molecular Drug Biochemistry and Therapy, 06120 Halle, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.affiliation: Institute of Mathematics, Lehrstuhl für Statistik und Wahrscheinlichkeitstheorie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Janssen
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoyer
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Bioanalytik, Hochschule für Angewandte Wissenschaften, Coburg, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Funke
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D005287:Ferredoxin-NADP Reductase / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology; D066263:Protein Aggregation, Pathological / Q000188:drug therapy*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; C534952:D3 peptide; D009842:Oligopeptides; C528560:affibody protein ZAbeta3; D013654:Taurine; C009217:scyllitol; D007294:Inositol; C001355:tramiprosate; D002392:Catechin; C045651:epigallocatechin gallate; D005287:Ferredoxin-NADP Reductase