Signal-enhanced detection of p-tau181 in human plasma as a biomarker for Alzheimer's disease using a multi-channel impedance analyzer with nanoliposome amplification.

Alzheimer's disease (AD), caused by amyloid-β (Aβ) aggregation-derived senile plaques, is among the most prevalent neurodegenerative disorders. Recently, Roche and Lilly announced the development of an AD diagnosis that utilizes phosphorylated tau (p-tau) and apolipoprotein E epsilon 4 allele as biomarkers, rather than Aβ. Additionally, the National Institute on Aging and Alzheimer's Association Research Framework suggests that p-tau molecules can serve as critical biomarkers for AD diagnosis. Here, we quantified p-tau181 in human plasma using a novel electrochemical assay method called the Electrical-Immunosorbent Assay (El-ISA), which employs a multichannel impedance analyzer (ToAD) with a 96-interdigitated microelectrode sensor array. The El-ISA partially follows the typical immunological sandwich assay process, quantitatively measuring the residual detection probes after the immunoreaction. The clinical performance of the El-ISA was evaluated using approximately 60 samples of human blood plasma, and its diagnostic accuracy was assessed based on clinical diagnostic data. Furthermore, impedance signals were amplified for protein quantification at the pg/mL level in human plasma by employing biotinylated nanoliposomes. We anticipate that the ToAD/El-ISA will evolve into a clinical in vitro diagnostic device for p-tau-based AD diagnosis in human blood.