The present study strongly suggests that the PSEN1 H163Y mutation has a reduced penetrance in brother B. This is supported by a longitudinal follow-up of the subject over 22 years, starting at the age of 43 (8 years before expected symptom onset) and ending at the age of 65 (14 years past the expected symptom onset), and his remaining amyloid-β biomarker-negative until the last time point with available biomarker assessment (age 60 years) and showing no cognitive decline on neuropsychological tests at the age of 65. The gene discussed is PSEN1; the disease is Mental deterioration.