PSEN1 and Alzheimer disease: The accumulation of Aβ is a hallmark pathological feature in both extensively studied autosomal dominant AD and sporadic late-onset AD patients.110 Aβ originates from the processing of the APP, a transmembrane glycoprotein, through its sequential cleavage by β-secretase and γ-secretase (a multiprotein complex with PS1 or PS2 as catalytic subunits).