PSEN1 and Mental deterioration: In APP/PS1 mice, amyloid plaques develop in the cortex already at 2 months of age (Radde et al., 2006), and neurons of cortical Layer 5 are the earliest affected, causing age-dependent impairment of synaptic plasticity, synapse loss and cognitive decline (Crouzin et al., 2013; Seo et al., 2014; Colié et al., 2017; Li K. et al., 2019).