More importantly, a recent case report of a PSEN1 E280A patient, also carrying the ApoE Christchurch (R136S) mutation, showed three decades of delayed onset of cognitive impairment together with high Aβ and low Tau pathology as determined with PET, supporting our hypothesis of pTau pathology as the main determinant factor in AoO in FAD [3]. This evidence concerns the gene APOE and Cognitive impairment.