Linkage analyses (1996) identified two highly homologous genes – PSEN1 and PSEN2 – that might be involved in the onset of AD.19,20 The structures of PSEN1 and PSEN2 are similar, with a homology of 67%. Both of them contain 12 exons with ten coding exons (exons 3–12) for a protein of ∼450 amino acids. Presenilin 1 (PS1) and presenilin 2 (PS2) proteins are transmembrane (TM) proteins with at least seven TM domains.19 The function of presenilins was first described by Wolfe et al, who proposed that two transmembrane aspartate (257 and 385) residues in PS1 are critical in gamma secretase activity.20 Most AD risk-factor mutations have been detected in PSEN1 (approximately 30%–70% of early onset FAD), which is located on chromosome 14. More than 180 mutations were found in PSEN1 in association with FAD, but they might be involved in sporadic AD or LOAD.14 Patients with PSEN1 mutations might develop AD symptoms in their 40s or early 50s, with a few cases occurring in persons in their late 30s and early 60s. Several missense mutations in PSEN1 can increase the
