PSEN1 and Alzheimer disease: Using Förster resonance energy transfer (FRET)-based imaging techniques we have previously shown that familial AD mutations in PS1 increase the proximity of PS1 N-terminus (NT) to C-terminus (CT) or to the large cytoplasmic loop domain, causing the so called ‘closed’ pathogenic PS1 conformation (Berezovska et al., 2005; Uemura et al., 2009).