PSEN1 and Alzheimer disease: The ε4 allele of APOE is the strongest genetic risk factor for AD.16,17 In addition to the common variants, several rare variants of APOE have been identified, including the APOE Christchurch (APOECh) variant (R136S),18 the APOE3-Jacksonville variant (V236E),19 and the APOE4 R251G variant.20 Recently, researchers found that an individual harboring the PSEN1 E280A mutation from the Paisa PSEN1 E280A kindred showed delayed onset of AD as shown by the limited development of Tau pathology despite the presence of excess amyloid plaques.