Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay

Abstract

Still, there is need for significant improvements in reliable and accurate diagnosis for Alzheimer's disease (AD) at early stages. It is widely accepted that changes in the concentration and conformation of amyloid-β (Aβ) appear several years before the onset of first symptoms of cognitive impairment in AD patients. Because Aβ oligomers are possibly the major toxic species in AD, they are a promising biomarker candidate for the early diagnosis of the disease. To date, a variety of oligomer-specific assays have been developed, many of them ELISAs. Here, we demonstrate the sFIDA assay, a technology highly specific for Aβ oligomers developed toward single particle sensitivity. By spiking stabilized Aβ oligomers to buffer and to body fluids from control donors, we show that the sFIDA readout correlates with the applied concentration of stabilized oligomers diluted in buffer, cerebrospinal fluid (CSF), and blood plasma over several orders of magnitude. The lower limit of detection was calculated to be 22 fM of stabilized oligomers diluted in PBS, 18 fM in CSF, and 14 fM in blood plasma.

Blood Amyloid-β Oligomerization as a Biomarker of Alzheimer’s Disease: A Blinded Validation Study

“…Aβ oligomers, playing a key-role in AD pathogenesis, have become a promising candidate for AD diagnosis. Efforts to measure Aβ oligomers in humoral fluids are currently underway (5)(6)(7). However, cost-effective and non-invasive diagnostic methods to detect Aβ oligomers are not currently available in clinical practice.…”

The reuse of public datasets in the life sciences: potential risks and rewards

“…While the scientific community and society are profiting most from public datasets, there are additional benefits of open access for authors themselves ( McKiernan et al, 2016 ; Leitner et al, 2016 ; Ali-Khan, Harris & Gold, 2017 ). Researchers can build a reputation by generating high quality and well-documented datasets.…”

Advancements of the sFIDA method for oligomer‐based diagnostics of neurodegenerative diseases

“…Using total internal reflection (TIRF) microscopy, the glass surface is scanned and pixels with intensity values above given cutoffs and at exactly the same position in both channels are counted for each image and considered as colocalized, where the number of colocalized pixels is referred to as “sFIDA readout” . Based on the application of a suitable calibration standard of known concentration and linear regression, the concentration of Aβ oligomers in the sample is calculated from the sFIDA readout.…”