Interface engineering of microelectrodes toward ultrasensitive monitoring of β-amyloid peptides in cerebrospinal fluid in Alzheimer's disease

Ultrasensitive detection of monomeric beta-amyloid peptides is of fundamental significance for studying the pathological progression of Alzheimer's disease (AD). In this article, by facilely engineering a gold microelectrode interface, we developed a novel electrochemical biosensor for sensitive and selective monitoring of beta-amyloid peptide (A beta) monomers in cerebrospinal fluid (CSF). Through specific Cu2+-A beta-hemin coordination, A beta directed the assembly of Cu2+-PEI/AuNPs-hemin nanoprobes into network aggregates on a microelectrode interface, which promoted the enrichment of A beta monomers on the microelectrode. Furthermore, the AuNP aggregate promotes the deposition of silver nanoparticles, which were utilized for the electrochemical stripping analysis of the A beta monomer. The proposed method displayed ultra-sensitivity for A beta monomers with the detection limit down to 0.2 pM. Besides, high selectivity toward A beta monomers was observed. These remarkable analytical performances render the electrochemical biosensor useful for evaluating the dynamic change of A beta monomer level in CSF of live mice with AD, promoting the investigation of the role that A beta monomers play in brain events.