Utilizing the Scanometric Immunoassay for the Ultrasensitive Detection of Aβ-42 Oligomers for the Early Detection of Alzheimer's DiseasePublic Deposited
Alzheimer’s disease (AD) is one of the most common forms of dementia, with no current definitive premortem diagnosis. Amyloid beta-peptide derived diffusible ligands, known as ADDLs, have become a key link in the AD specificity for memory loss and are a potential biomarker for AD. In order to develop an early diagnostic tool, ADDLs are a target of new ultrasensitive protein assays, such as the scanometric immunoassay (SIA). To utilize the SIA for ADDL detection, different detection antibodies and oleocanthal treatments were examined to improve the sensitivity of the assay. The oleocanthal treatments reduced background in the lower concentration wells and had no apparent effect on the detection probes. Control transgenic mouse brain extracts, control human brain extracts, as well as high-performance liquid chromatography (HPLC) fractionated extracts were also studied as part of the transition toward examining biological samples. Using the SIA, ADDLs were detected in both HPLC-fractionated control and AD human brain extracts using NU-1 as the capture antibody. This is noteworthy because the dot-blot assays on these samples had no signals for any fraction. Furthermore, the SIA was able to detect a 4-fold difference between the control and AD nonfractionated samples, while the dot-blot assay had only faint detections when using NU-1. These results make the SIA promising for detecting ADDLs in biological samples.