Fig. 11.

Capture of receptors for Aβ oligomers in nanodiscs and a high-throughput assay to screen for unknown therapeutic targets. Top Schematic of Nanodisc formation using synaptic plasma membranes. Each Nanodisc consists of a discoidal lipid bilayer stabilized by artificial membrane scaffold proteins (MSP) with His tags. A small fraction of the population contains AβO-binding proteins. His tags on Nanodiscs and biotin on AβOs provide a means for conducting binding assays. Bottom Aurin tricarboxylic acid (ATA) potently reduces synaptic AβO accumulation in culture. ATA was assayed at 1 µM for a preventative effect on AβO accumulation at synapses in cultured rat hippocampal neurons. Images shown are of typical neurons after treatment with AβOs (left panel) or AβOs following ATA pre-treatment (right panel). AβOs are shown in green, neurons identified by β3 tubulin fluorescence are white, and DAPI is blue to indicate nuclei. Selected neurites are enlarged below each image to illustrate the distribution of bound AβO. Scale bar 10 µm. Adapted from Wilcox et al. [180]