APOE and Alzheimer disease: On the other hand, the inclusion of control participants is really complex because it is difficult to create a sample of controls with no risk variables if we consider that as we have mentioned above, AD is a multifactorial disease of which we do not know many factors or their interactions yet [28], therefore we have delimited participants to an age-matched population as control, with no family history of AD or vascular dementia and without any ε4 allele for the ApoE gene.