PSEN1 and Alzheimer disease: APOEε4 has been suggested to modulate the activity of PSEN1 in this regard; when there is a disruption in PSEN1 caused by a specific genetic variant (such as the PSEN1 variant), the presence of APOEε4 could potentially interact with this alteration and have an additional impact on Aβ generation, thereby modifying the risk of developing AD [38].