LED-based interferometric reflectance imaging sensor for the detection of amyloid-β aggregation

Abstract

Self-aggregation of amyloid-β (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). Small molecule inhibitors of Aβ fibril formation reduce the Aβ-mediated neurotocixity. In this report, the interaction of amyloid-β (Aβ) with well-described modulators, (-)epigallocatechin-3-gallate (EGCG) and Zn(ii), was detected using a LED-based interferometric reflectance imaging sensor (LED-IRIS) in a high-throughput and real-time format. Nucleation-based fibril growth strategy was employed, as the "seeds" of Aβ were prepared in the presence of EGCG and Zn(ii). The seeds were then covalently immobilized on the chip surface. Using microfluidics, Aβ oligomers were exposed onto the seeds resulting in the elongation of fibrils, which was detected as the increase in the spot height. Monitoring the changes on the chip surface enabled to detect the efficacy of modulators to inhibit or facilitate the growth of Aβ fibrils. The proof-of-concept study reported here introduces a novel platform to facilitate the screening of small molecules towards the discovery of promising AD therapeutics.