Highly penetrant rare variants in amyloid precursor protein (APP), and presenilin 1 and 2 (PSEN1, PSEN2), and SORL1 are associated with early-onset AD (onset age < 60 years) and often in an autosomal dominant pattern, but other variants in these genes are associated with the common form of late-onset AD (onset age > 60 years). Here, PSEN1 is linked to Alzheimer disease.