Abstract
Determination of the conformation (monomer, oligomer, or fibril) of amyloid peptide aggregates in the human brain is essential for the diagnosis and treatment of Alzheimer’s disease (AD). Accordingly, systematic investigation of amyloid conformation using analytical tools is essential for precisely quantifying the relative amounts of the three conformations of amyloid peptide. Here, we developed a reduced graphene oxide (rGO) based multiplexing biosensor that could be used to monitor the relative amounts of the three conformations of various amyloid-β 40 (Aβ40) fluids. The electrical rGO biosensor was composed of a multichannel sensor array capable of individual detection of monomers, oligomers, and fibrils in a single amyloid fluid sample. From the performance test of each sensor, we showed that this method had good analytical sensitivity (1 pg/mL) and a fairly wide dynamic range (1 pg/mL to 10 ng/mL) for each conformation of Aβ40. To verify whether the rGO biosensor could be used to evaluate the relative amounts of the three conformations, various amyloid solutions (monomeric Aβ40, aggregated Aβ40, and disaggregated Aβ40 solutions) were employed. Notably, different trends in the relative amounts of the three conformations were observed in each amyloid solution, indicating that this information could serve as an important parameter in the clinical setting. Accordingly, our analytical tool could precisely detect the relative amounts of the three conformations of Aβ40 and may have potential applications as a diagnostic system for AD.
Highlights
Amyloid-β (Aβ) peptides, including amyloid-β 40 (Aβ40) and Aβ42, are crucial hallmarks of Alzheimer’s disease (AD), and excessive production of Aβ and its deposition at the brain surface cause the various symptoms of AD [1,2]
We developed a reduced graphene oxide (rGO) biosensor that could be used to monitor the relative amounts of the three conformations in various amyloid fluids (Figure 1a)
For specific detection of conformational changes in Aβ40, our sensor system was based on electrical measurement in which the resistance of the rGO thin film was monitored when Aβ40 was added
Summary
Amyloid-β (Aβ) peptides, including Aβ40 and Aβ42, are crucial hallmarks of Alzheimer’s disease (AD), and excessive production of Aβ and its deposition at the brain surface cause the various symptoms of AD [1,2]. The concentrations of both Aβ40 and Aβ42 are related to the progression of AD [9,10], accurate measurement of Aβ40 is important. Even if total Aβ levels are increased, the Aβ42 level in the Cerebrospinal fluid (CSF) can decrease unexpectedly due to deposition of aggregated Aβ42 in the brain [10,11]. The detection of Aβ40 levels may be an excellent strategy for blood-based examination of nonfamilial AD because of the higher concentration of Aβ40 in serum [8]. Accurate detection of Aβ40 is necessary to correctly diagnose familial AD. The concentration ratio of Aβ42/Aβ40 is relevant to the diagnosis of AD, and accurate detection of Aβ40 is important for estimation of this ratio [12,13]
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