TY  - JOUR
AU  - Bannach, Oliver
AU  - Pils, Marlene
AU  - Dybala, Alexandra
AU  - Rehn, Fabian
AU  - Blömeke, Lara
AU  - Bujnicki, Tuyen
AU  - Kraemer-Schulien, Victoria Maria
AU  - Hoyer, Wolfgang
AU  - Riesner, Detlev
AU  - Willbold, Dieter
TI  - Development and implementation of an internal quality control sample to standardize oligomer-based diagnostics of Alzheimer's disease
JO  - Diagnostics
VL  - 13
IS  - 10
SN  - 2075-4418
CY  - Basel
PB  - MDPI
M1  - FZJ-2023-02027
SP  - 1702 -
PY  - 2023
AB  - Protein misfolding and aggregation are pathological hallmarks of various neurodegenerative diseases. In Alzheimer’s disease (AD), soluble and toxic amyloid-β (Aβ) oligomers are biomarker candidates for diagnostics and drug development. However, accurate quantification of Aβ oligomers in bodily fluids is challenging because extreme sensitivity and specificity are required. We previously introduced surface-based fluorescence intensity distribution analysis (sFIDA) with single-particle sensitivity. In this report, a preparation protocol for a synthetic Aβ oligomer sample was developed. This sample was used for internal quality control (IQC) to improve standardization, quality assurance, and routine application of oligomer-based diagnostic methods. We established an aggregation protocol for Aβ1–42, characterized the oligomers by atomic force microscopy (AFM), and assessed their application in sFIDA. Globular-shaped oligomers with a median size of 2.67 nm were detected by AFM, and sFIDA analysis of the Aβ1–42 oligomers yielded a femtomolar detection limit with high assay selectivity and dilution linearity over 5 log units. Lastly, we implemented a Shewhart chart for monitoring IQC performance over time, which is another important step toward quality assurance of oligomer-based diagnostic methods.
LB  - PUB:(DE-HGF)16
C6  - 37238187
UR  - <Go to ISI:>//WOS:000998096700001
DO  - DOI:10.3390/diagnostics13101702
UR  - https://juser.fz-juelich.de/record/1007358
ER  -