High-Performance Extended-Gate Field-Effect Transistor for Kinase Sensing in Aβ Accumulation of Alzheimer's Disease

An amyloid-beta peptide (A beta) is generally believed to be a pathological marker of Alzheimer's disease (AD), but it is still of great significance to explore the upstream and downstream relationship of A beta in AD. It is previously reported that c-Abl, a nonreceptor tyrosine kinase, can be activated by A beta, but the interaction between A beta and c-Abl is still unknown. Herein, an extended-gate field-effect transistor (EG-FET)-based sensor has been developed to monitor the level of c-Abl with high sensitivity and selectivity. Our peptide-functionalized EG-FET sensor as the signal transducer can follow c-Abl activity with electron transfer by its specific phosphorylation. The sensor presents a good linear correlation over c-Abl concentrations of 1 pg/mL to 3.05 mu g/mL. The sensor was successfully applied to quantify c-Abl activity in the brain tissue of AD transgenic mice, and the interaction between c-Abl and A beta in AD mice was explored by administering the c-Abl inhibitor (imatinib) and the agonist (DPH). Our work is expected to provide an important reference for early diagnosis and treatment of AD.

Automated summary

Exploring the upstream and downstream relationship of Aβ in Alzheimer's disease (AD) is of great significance. In this study, a peptide-functionalized EG-FET sensor was developed to monitor c-Abl level with high sensitivity and selectivity. The sensor was successfully used to quantify c-Abl activity in AD transgenic mice and explore the interaction between c-Abl and Aβ.