Development of peptide aptamers as alternatives for antibody in the detection of amyloid-beta 42 aggregates

Abstract

Alzheimer's disease (AD) causes cognitive impairment and serious social isolation. However, there are no effective treatments and even no established confirmatory diagnostic tools for the disease. Amyloid beta (Aβ) aggregation in the brain is the best-known pathognomonic mechanism of AD, so various methods for Aβ detection have been developed for the diagnosis of this disease. We synthesized two novel, ultra-sensitive peptide probes specialized in detecting Aβ aggregates, and examined their potential for future diagnostic application. The peptides are produced through phage high-throughput screening (HTS) and amplified through a serial process called biopanning, which is a repeating method of elution and amplification of probes. We picked phages specific for amyloid from two kinds of phage display. The synthesized peptides were confirmed to have excellent binding affinity to Aβ aggregates, by immunohistochemical staining and western blotting using the brains of 3X transgenic (Tg) AD mice at different stages (5-7, 12-17 months old) of AD severity. In the present study, it was confirmed that newly developed amyloid-binding peptides could be used as novel probes for the detection of Aβ aggregates, which can be used for clinical diagnosis of AD in the future.

Keywords: Alzheimer's disease; Aβ42; Early diagnosis; Peptide aptamer; Phage display; Probe screening.