Small molecule therapeutic candidates can prevent or displace Abeta oligomer binding to mature primary hippocampal and cortical cultures (21DIV).

<p>Abeta synthetic oligomers were added to neuronal cultures (0.5 µM total Abeta concentration) for 40 min prior to (<b>A–F</b>) or following (<b>G–L</b>) addition of compounds and bound Abeta was detected by immunofluorescence. <b>A, G</b> Vehicle controls with no Abeta show background fluorescence. <b>C, I</b>, 15 µM CT0109, <b>D, J</b>, CT0093, <b>E, K</b>, CT01344, or <b>F, L</b>, CT01346 show that immuno-fluorescence for punctate binding of Abeta oligomers to neurites is blocked by all four compounds. Accompanying MAP2 panel shows similar density of neurons from right-hand side for each Abeta image. Scale bar = 20 µm. <b>M</b>, Quantification of Abeta immunofluorescence shows that pretreatment with CT0093 prevents Abeta binding in a dose-dependent manner fitting a single site binding model (r2 = 0.79, N = 8, EC50 = 2.2±2.4 µM). <b>N</b>, CT01344 displaces pre-bound Abeta binding in a dose-dependent manner fitting a single site binding model (r2 = 0.92, N = 8, EC50 = 3.9±1.8 µM). * = statistically different than control, P<0.05, Student's t-test.