PSEN1 and Alzheimer disease: We recently found that apolipoprotein E isoforms bind with differential affinity to HSPG, corresponding to their suggested risk for AD (ApoE4 > 3 > 2), that it binds with extremely low affinity to the rare ApoE Christchurch variant which we found to be associated with an exceptionally low risk of AD dementia in a Presenilin 1 (PSEN1) E280A mutation carrier from the world’s largest autosomal dominant AD (ADAD) kindred, and that it binds with extremely low affinity to wild type APOE in the presence of an antibody bound to the ApoE Christchurch binding domain.