Fig. 1

PS1 conformation and Aβ production change upon KCl or glutamate treatment. a Schematic representation of the “open” (left) and “closed” (right) PS1 conformation; green and red circles represent green fluorescent protein (GFP) and red fluorescence protein (RFP) fused to PS1 NT and L6-7, respectively, to generate FRET reporter probe. b Time-lapse recording of PS1 conformational changes in live neurons transfected with GFP-PS1-RFP FRET reporter probe and treated with KCl, glutamate, or water control. The Spectral FRET data are presented as a change in the RFP/GFP ratio, 50 to 100 neurons were analyzed for each condition; the graph shows mean ± SEM; detailed statistical analysis of the Spectral FRET data evaluation is described in the Methods. c Time-lapse recording of Oregon Green 488 BAPTA-1 AM fluorescence intensity changes reflecting intracellular calcium load in primary neurons treated with KCl, glutamate, or water control. Three independent experiments, mean ± SEM. d ELISA measurements of secreted Aβ40 and Aβ42 in conditioned-medium collected from KCl (KCl+) or H₂O (KCl-) treated mouse cortical neurons. The Aβ levels determined in pmol were normalized to the amount of total protein [g] extracted from the cells in the corresponding well. Data are presented as mean% ± SEM, n = 4; 100 % = 91.11 pmol/g for Aβ40 and 11.04 pmol/g for Aβ42. Statistical significance was determined using the Mann-Whitney U test, *p < 0.05. PS1 presenilin 1, Aβ amyloid β, NT N-terminus, FRET Förster Resonance Energy Transfer