title: Biofunctionalized Silica Nanoparticles: Standards in Amyloid-β Oligomer-Based Diagnosis of Alzheimer's Disease.
abstract: Amyloid-β (Aβ) oligomers represent a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, state-of-the-art methods for immunodetection of Aβ oligomers in body fluids show a large variability and lack a reliable and stable standard that enables the reproducible quantitation of Aβ oligomers. At present, the only available standard applied in these assays is based on a random aggregation process of synthetic Aβ and has neither a defined size nor a known number of epitopes. In this report, we generated a highly stable standard in the size range of native Aβ oligomers that exposes a defined number of epitopes. The standard consists of a silica nanoparticle (SiNaP), which is functionalized with Aβ peptides on its surface (Aβ-SiNaP). The different steps of Aβ-SiNaP synthesis were followed by microscopic, spectroscopic and biochemical analyses. To investigate the performance of Aβ-SiNaPs as an appropriate standard in Aβ oligomer immunodetection, Aβ-SiNaPs were diluted in cerebrospinal fluid and quantified down to a concentration of 10 fM in the sFIDA (surface-based fluorescence intensity distribution analysis) assay. This detection limit corresponds to an Aβ concentration of 1.9 ng l-1 and lies in the sensitivity range of currently applied diagnostic tools based on Aβ oligomer quantitation. Thus, we developed a highly stable and well-characterized standard for the application in Aβ oligomer immunodetection assays that finally allows the reproducible quantitation of Aβ oligomers down to single molecule level and provides a fundamental improvement for the worldwide standardization process of diagnostic methods in AD research.
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Hülsemann
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zafiu
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kühbach
authors.affiliation: Forschungszentrum Jülich, ZEA-3, Zentralinstitut für Engineering, Elektronik und Analytik, Jülich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lühmann
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Herrmann
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Luriano
authors.initials: L
authors.lastname: Peters
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Linnartz
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Willbold
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Kravchenko
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulawik
authors.affiliation: Forschungszentrum Jülich, ZEA-3, Zentralinstitut für Engineering, Elektronik und Analytik, Jülich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Willbold
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.|Heinrich-Heine-Universität Düsseldorf, Institut für Physikalische Biologie, Düsseldorf, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bannach
authors.affiliation: Forschungszentrum Jülich, ICS-6, Institut für Strukturbiochemie, Jülich, Germany.|Heinrich-Heine-Universität Düsseldorf, Institut für Physikalische Biologie, Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000138:chemical synthesis / Q000276:immunology; D000939:Epitopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D056951:Photoelectron Spectroscopy; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000138:chemical synthesis; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water
chemical_list: D016229:Amyloid beta-Peptides; D000939:Epitopes; D014867:Water; D012822:Silicon Dioxide
keywords: Alzheimer’s disease diagnosis; Aβ oligomer standards; assay standardization; biofunctionalized nanoparticles