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

Ultrasensitive detection of monomeric β-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 β-amyloid peptide (Aβ) monomers in cerebrospinal fluid (CSF). Through specific Cu²⁺-Aβ-hemin coordination, Aβ directed the assembly of Cu²⁺-PEI/AuNPs-hemin nanoprobes into network aggregates on a microelectrode interface, which promoted the enrichment of Aβ monomers on the microelectrode. Furthermore, the AuNP aggregate promotes the deposition of silver nanoparticles, which were utilized for the electrochemical stripping analysis of the Aβ monomer. The proposed method displayed ultra-sensitivity for Aβ monomers with the detection limit down to 0.2 pM. Besides, high selectivity toward Aβ monomers was observed. These remarkable analytical performances render the electrochemical biosensor useful for evaluating the dynamic change of Aβ monomer level in CSF of live mice with AD, promoting the investigation of the role that Aβ monomers play in brain events.