Development of a Low-Molecular-Weight Aβ42 Detection System Using a Enzyme-Linked Peptide Assay

Abstract

Alzheimer’s disease (AD) is a degenerative brain disease that is the most common cause of dementia. The incidence of AD is rapidly rising because of the aging of the world population. Because AD is presently incurable, early diagnosis is very important. The disease is characterized by pathological changes such as deposition of senile plaques and decreased concentration of the amyloid-beta 42 (Aβ42) peptide in the cerebrospinal fluid (CSF). The concentration of Aβ42 in the CSF is a well-studied AD biomarker. The specific peptide probe was screened through four rounds of biopanning, which included the phage display process. The screened peptide showed strong binding affinity in the micromolar range, and the enzyme-linked peptide assay was optimized using the peptide we developed. This diagnostic method showed specificity toward Aβ42 in the presence of other proteins. The peptide-binding site was also estimated using molecular docking analysis. Finally, the diagnostic method we developed could significantly distinguish patients who were classified based on amyloid PET images.

Computer-Assisted Design of Peptide-Based Radiotracers

“…Our journey in the report of the most recent application of CADD in peptide-based radiotracers starts with a contemporary application of the molecular docking analyses performed by Kim et al [ 20 ]. In this study, in silico investigation has been used to identify the overproduction of a specific protein responsible for Alzheimer’s disease.…”

Chiral nanomaterial-based approaches for diagnosis and treatment of protein-aggregated neurodiseases: current status and future opportunities

“…Although these biomolecules offered selective binding affinity with Aβ, disadvantages such as the stability of these biomolecules and the influence of steric hindrance along with tedious storage conditions limit their application. 30,31 Since Aβ contains a cascade of chirality and any change in the chiral environment either through variation in amino acids or through variation in isomerization and epimerization can lead to protein aggregation. Some recent reports have suggested that any change in d -Asp23 caused Aβ 42 (42 residues long) formation of β-lamellar fibers; similarly, d -serine levels were higher in the cerebrospinal fluid of AD patients, thus exploring that chirality-mediated strategies can become very promising for the inhibition of protein fibrils through “chiral–chiral” interactions between proteins and chiral nanomaterials via hydrophobic interaction, electrostatic interaction, and hydrogen bonding.…”

Aggregation-Induced Electrochemiluminescence Based on a Zinc-Based Metal–Organic Framework and a Double Quencher Au@UiO-66-NH2 for the Sensitive Detection of Amyloid β 42 via Resonance Energy Transfer

“…Therefore, the accurate monitoring of Aβ42 is essential for the early diagnosis of AD. Several methods for the detection of Aβ42 have been reported, such as enzyme-linked immunoassay (EILSA), electrochemistry (EC), photochemistry, multiplex biosensors, and electrochemiluminescence (ECL) . Compared to most methods, ECL has a high sensitivity, simple devices, and excellent controllability.…”