earticle

영어

The principal histopathological feature of Alzheimer’s disease is the presence of β-amyloid (Aβ) aggregates in the brain, and researchers believe that various environmental factors play significant roles in the conformational change of Aβ peptides. Therefore, discovering a rapid and convenient analytical method of evaluating the environmental factors on Aβ aggregation would have a considerable impact. Herein we report our development of a novel microfluidic screening system enabling high-throughput analysis, low-consumption of reagents, and short analytical time. Microchannels were immobilized with Aβ monomers via N-hydroxysuccinimide ester activation, and then a fresh Aβ monomer solution mixed with different small molecules was continuously introduced into the microchannels. In this work, we investigated (1) the temporal evolution of Aβ aggregation within microchannels, (2) the high-throughput screening of the inhibitory effect of twelve small molecules against Aβ aggregation, and (3) the effect of different metal ions (Fe3+, Cu2+, Zn2+, and Al3+) on Aβ aggregation by using ThT-induced fluorescence microscopy and ex situ atomic force microscopy. The microfluidic system should contribute to a simultaneous analysis of multiple environmental factors in a parallel manner and to screen therapeutic small molecules prior to their in vivo evaluation.