P009 - AN IN VITRO PLATFORM FOR MODELING AND MEASURING THE OLIGOMER STATE IN THE AMYLOID Β GROWTH DYNAMICS (ID 2212)
Abstract
Aims
A variety of different amyloid β (Aβ) protein aggregates forms in Alzheimer’s disease (AD), and this aggregation pathway has been linked with severity of AD. Therefore, monitoring the process of Aβ aggregation could facilitate the identification of pathogenic indicators that enable early-stage diagnosis and treatment.
Methods
We show a strategy for label-free terahertz (THz) optical monitoring the aggregation dynamics of Aβ proteins—from monomers to fibrils—under physiological conditions including body temperature and incubation medium (e.g., buffer versus Matrigel) with a nanomolar detection limit using near-field THz spectroscopy.
Results
We clearly reveal the rate-limiting, stepwise nature of this aggregation process, identifying three steady states for polymerization of monomers, oligomers, and fibrils, separated by two transition states. We verify the existence of these states by analyzing sample morphologies with atomic force microscopy. We further show that the transition time and growth rate of each steady state vary with physiological conditions and are modeling a universal equation for full growth pathway of Aβ aggregation.
Conclusions
We anticipate that our method for the label-free detection of Aβ oligomer state could ultimately facilitate the earlier clinical diagnosis of AD with drop-sized physiological samples.
