APP and Alzheimer disease: Of the five positive individuals of the AD cohort, 4 (1%), (Probands 1, 2, 3 and 5) originated from the referral series of 381 patients for a diagnostic test of AD gene mutation and screened for APP, PSEN1, PSEN2 and 1 (0.2%), (Proband 4) originated from 492 patients comprising a collection of patients thought to have AD but with insufficient clinical evidence to justify screening of causal genes.