Description: Biofunctionalized Silica Nanoparticles: Standards in Amyloid-β Oligomer-Based Diagnosis of Alzheimer’s Disease

This title appears in the Scientific Report : 2016

Biofunctionalized Silica Nanoparticles: Standards in Amyloid-β Oligomer-Based Diagnosis of Alzheimer’s Disease

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 quantitati...

Personal Name(s):	Hülsemann, Maren
	Zafiu, Christian / Kühbach, Katja / Lühmann, Nicole / Herrmann, Yvonne / Peters, Luriano / Linnartz, Christina / Willbold, Johannes / Kravchenko, Kateryna / Kulawik, Andreas / Willbold, Sabine / Bannach, Oliver / Willbold, Dieter (Corresponding author)
Contributing Institute:	Analytik; ZEA-3 Strukturbiochemie; ICS-6
Published in:	Journal of Alzheimer's disease, 54 (2016) 1, S. 79 - 88
Imprint:	Amsterdam IOS Press 2016
DOI:	10.3233/JAD-160253
PubMed ID:	27472876
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.3233/JAD-160253 in citations.

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.