Aβ protein growth monitoring by structure-specific label-free THz spectroscopy.

Abstract

A variety of different amyloid β (Aβ) protein aggregate forms have been linked with severity of Alzheimer's disease (AD) and its aggregation pathway can be a primary biomarker for diagnosis. Our group recently developed the water-based near-field terahertz (THz) spectroscopy technique to measure Aβ in solution (Heo et al., ACS Nano, 2020, 14 (6), 6548-6558). By noting monotonic conductance change with frequency in monomers following Drude tail and nonlinear conductance behaviors in oligomers and fibrils adopting the localization parameter in Smith model, we derived a structure-specific discrete metric that we termed dementia quotient (DQ), which is a structurally defined biophysical index of Aβ aggregation state with modified Drude-Smith model. Furthermore, we investigate Aβ protein dynamics to identify various morphological phase transitions from monomers to fibrils by monitoring the structure-specific DQ values under physiological conditions including body temperature and incubation medium (e.g., buffer versus Matrigel). Our method could ultimately facilitate the early AD diagnosis by clearly detecting of Aβ oligomer state in a nanomolar concentration (∼nm) of the proteins.