PSEN2 and Alzheimer disease: The accumulation of Aβ peptide, which is produced from APP via sequential cleavage by β-secretase and γ-secretase, is thought to be a causative factor of AD pathology [36,54], and the elevation of Aβ was found to result from pathogenic mutations in APP, PSEN1 and PSEN2. PSEN1 encodes a subunit of γ-secretase that releases soluble APP from the cellular membrane.