Functionalized Graphene-Based Electrochemical Array Sensors for the Identification of Distinct Conformational States of Amyloid Beta in Alzheimer's Disease

Abstract

Aβ oligomers have been widely accepted as significant biomarkers for Alzheimer’s disease (AD) detection, monitoring, and therapy since they are highly correlated with AD development. As two major forms, the research of Aβ40 and Aβ42 draw increasing attention in recent decades, where many methods have been constructed. However, these methods are time-consuming, complicated to operate, and require prior knowledge of the structural information of each form of Aβ. In this work, we constructed a functionalized graphene array sensing platform, which can discriminate different Aβ forms, the mixture of various Aβ forms, and different ratios of Aβ42 to Aβ40 efficiently. 100% identification through the combination of dual probes was achieved successfully, indicating the super diagnostic capacity of the constructed sensor array. Furthermore, it also exhibited excellent performance for screening Aβ inhibitors and metal chelators. The strategy utilizes the infinitesimal general discrepancy instead of specific biomarker recognition, exhibiting the advantage of no requirement to know the exact information about the specific ligand and receptor in advance, which is promising to be widened for the other biosensing detection fields.

Keywords: Alzheimer's disease, Aβ42, Aβ40, Aβ inhibitors, Metal chelators, Electrochemical array sensors