期刊
SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-89004-x
关键词
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资金
- TKI research grant from Health Holland [LSHl17OO1]
- Gieskes-Strijbis Fonds
- Alzheimer Nederland [NL-17004]
- European Commission (Marie Curie International Training Network, JPND)
- Dutch Research Council (ZonMW)
- Weston Brain Institute
- Alzheimer Netherlands
- NCDC
- ZonMW Memorabel [73305095005]
- Alzheimer Nederland
Plasma biomarkers reflecting specific Abeta proteoforms can provide valuable insights into the treatment effects of Alzheimer's disease therapies. The newly developed Amyblood assays showed similar technical and clinical performance as commercial assays, but exhibited better specificity and selectivity, making them promising for monitoring treatment response in clinical trials.
Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer's disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa 'Amyblood' assays that measure full length Abeta(1-42) and Abeta(1-40) and compare their performance with two commercial assays. Linearity, intra- and inter-assay %CV were compared between Amyblood, Quanterix Simoa triplex, and Euroimmun ELISA. Sensitivity and selectivity were assessed for Amyblood and the Quanterix triplex. Clinical performance was assessed in CSF biomarker confirmed AD (n=43, 68 +/- 6 years) and controls (n=42, 62 +/- 5 years). Prototype and Amyblood showed similar calibrator curves and differentiation (20 AD vs 20 controls, p<0.001). Amyblood, Quanterix triplex, and ELISA showed similar linearity (96%-122%) and intra-assay %CVs (3.1%). A minor non-specific signal was measured with Amyblood of+2.4 pg/mL Abeta(1-42) when incubated with 60 pg/mL Abeta(1-40). A substantial non-specific signal of+24.7 pg/mL Abeta(x-42) was obtained when 40 pg/mL Abeta(3-42) was measured with the Quanterix triplex. Selectivity for Abeta(1-42) at physiological Abeta(1-42) and Abeta(1-40) concentrations was 125% for Amyblood and 163% for Quanterix. Amyblood and Quanterix ratios (p<0.001) and ELISA Abeta(1-42) concentration (p=0.025) could differentiate AD from controls. We successfully developed and upscaled a prototype to the Amyblood assays with similar technical and clinical performance as the Quanterix triplex and ELISA, but better specificity and selectivity than the Quanterix triplex assay. These results suggest leverage of this specific assay for monitoring treatment response in trials.
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