Further, in some MCI patients, most AD patients, and APP/PS-1 double transgenic mice, a reduction in flippase activity, responsible for translocating PS isoforms within synaptic bilayers is reduced resulting in the accumulation of PS at the outer leaflet of synaptosomal membranes (Bader Lange et al., 2008, 2010). Here, PSEN1 is linked to Alzheimer disease.