Apoptotic Proteolytic Cleavage of the Presenilins by Caspases
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Familial Alzheimer’s disease (FAD) is a genetically heterogeneous disorder that is caused by defects in at least three early onset genes (age of onset:<60 yr.): presenilin 2 (PS2 ) on chromosome 1 (1 ), presenilin 1 (PS1 ) on chromosome 14 (2 ), and amyloid protein precursor (APP ) on chromosome 21 (3 ,4 ). Mutations within the APP gene are responsible for only a small portion (<2%) of reported cases of FAD (5 ), whereas up to half of all early onset FAD cases are caused by mutations in the PSEN1 and PSEN2 genes (6 ,7 ).
