PSEN1 and Alzheimer disease: While AD is the most common form of dementia, only ~1%–5% of cases can be explained completely by genetic origin (Piaceri et al., 2013); this is most commonly related to mutations in amyloid precursor protein (APP) or presenilin 1/2 (PSEN1/PSEN2) that result in the overproduction of toxic β-amyloid peptides (Aβ) and an early-onset of disease symptoms (for reviews see Tanzi, 2012; Wu et al., 2012).