Figure 2

Lowering VAMP1 transcript and VAMP1 protein expression in primary neurons reduces Aβ secretion. Levels of Aβ40 and Aβ42 species secreted into the media were measured in A) mouse primary neurons subjected to shRNA-mediated knockdown of VAMP1 (VAMP1 shRNA) versus non-target neurons treated with scrambled shRNA (n = 7), and B) mouse primary neurons of transgenic mice with heterogeneous knockdown of VAMP1 (VAMP1+/-) versus Wild-type mice (n = 6). Media were tested for Aβ at day 4 (d4) and day 8 (d8) of neuronal culture. C) Soluble Aβ40 and Aβ42 were also measured in brain extracts from Wild-type and VAMP1+/- mice. Bars represent mean values across replicates. Error bars represent standard error of the mean. *p > 0.05, ***p < 0.0001 for t-test. Representative Western blot images showing reduced VAMP1 expression levels in the VAMP1 shRNA treated versus non-target neurons (A) and in brains of VAMP1+/- and VAMP1-/- versus wild-type mice (C) are shown.