Fabrication Of Graphene Oxide/gold Nanoparticles Hydrogel Biosensor And Its Application In The Detection Of Alzheimer’s Amyloid-beta Oligomers

Alzheimer’s disease(AD)is a common neurodegenerative disorder in old people and the most common cause of dementia.The accumulation of beta-amyloid interferes with the synapse function and contributes to the damage of neurons.Misfolding and aggregation of Aβ is the potential pathological mechanism of AD.Aβmonomers can assemble into Aβ oligomers(AβO)and fibrils,then distributed into the cerebrospinal fluid or blood circulation.AβO are considered to be the most neurotoxic form and more correlated with the severity of AD than insoluble aggregates.With regard to its close relation with AD development,AβO is considered a core biomarker for AD,especially in the early stage of AD.Here,a simple electrochemical biosensor using graphene oxide/gold nanoparticles(GO/GNPs1 and GO/GNPs2)hydrogel electrode has been developed to detect AβO.GO was synthesized from graphite by the modified Hummers method.The deposition of Au NPs on the GO/GNPs1 hydrogel was achieved by the edge defects(-OH,-COOH,etc.)in chemically modified graphene.GO possess ambipolar conduction type which may also contribute to this reduction of HAuCl4.The deposition of Au NPs on the GO/GNPs2 hydrogel was reduced by GO and NaBH4.The effects of the PrPc concentration and incubation time were investigated by EIS.We choose GO/GNPs1 and GO/GNPs2 hydrogel electrode as the AβO biosensor for two reasons:1.GO/GNPs1 and GO/GNPs2 hydrogel provides suitable conductivity for sensitive AβO detection;2.GNPs have high specific surface area and offer numerous adsorption sites to thiolated PrPC probe by Au-S bonding.Impedance spectroscopy was employed for AβO analysis.The specific binding between AβO and PrPC probe resulted in increased electron-transfer resistance.The GO/GNPsl-PrPc and GO/GNPs2-PrPc biosensor has been used to detect AβO in artificial cerebrospinal fluid(aCSF)or human blood plasma with satisfactory results.This biosensor has high specificity,which can selectively differentiate AβO from Aβmonomers or fibrils.Meanwhile,it is highly sensitive to detect as low as 0.1 pM AβO in aCSF or blood plasma to meet the requirements in clinical detection of AβO.The linear range for AβO detection is from 0.1 pM to 10 nM.This biosensor could be used as a cost-effective and non-invasive diagnostic tool for early diagnosis of AD.