Journal Article FZJ-2023-02027

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Development and implementation of an internal quality control sample to standardize oligomer-based diagnostics of Alzheimer's disease

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2023
MDPI Basel

Diagnostics 13(10), 1702 - () [10.3390/diagnostics13101702]

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Abstract: 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.

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Contributing Institute(s):
  1. Strukturbiochemie (IBI-7)
Research Program(s):
  1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2023
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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Open Access

 Datensatz erzeugt am 2023-05-09, letzte Änderung am 2024-01-18


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