Gelsolin bound β-amyloid peptides_(1-40/1-42): ELECTROCHEMICAL evaluation of levels of soluble peptide associated with Alzheimer's disease

A method for the highly sensitive determination of soluable β-amyloid peptides (Aβ_1-40/1-42) that employs a detection bioconjugate of HRP-Au-gelsolin as the electrochemical nanoprobe is presented. Contrary to previous detection notions that utilized antibodies, which could specifically recognize the N- or C-terminus of peptides, we demonstrate herein that the reported specific binding between gelsolin and Aβ might provide an alternative way to evaluate the peptides sensitively and selectively. The HRP-Au-gelsolin nanohybrid was designed by one-pot functionalization of Au nanaoparticles (NPs) with horseradishperoxidase (HRP) and gelsolin. Through a sandwich-type sensor array, soluble Aβ_1-40/1-42 were captured onto the array due to the interactions between targeted peptides and surface-confined gelsolin and electrochemical signals were amplified by abundant attachments of HRP labeled on AuNPs, which could specifically catalyse its substrate, 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H₂O₂ to give rise to measurable signals. The proposed gelsolin-bound Aβ methodology displayed satisfactory sensitivity and wide linear range towards Aβ_1-40/1-42 with a detection limit down to 28pM, which are verified to be sensitive-enough for the assessment of Aβ levels both in normal and Alzheimer's disease (AD) rat brains. Experimental results indicated that compared with normal group, soluble β-amyloid peptide levels in cerebrospinal fluid (CSF) and targeted brain tissues of AD rats all declined with differentiable degrees. In short, the newly unfolding strategy presents valuable information related to pathological events in brain and will exhibit a braw perspective for the early diagnosis of AD process.