Alzheimer’s Disease (AD) is characterized by progressive memory loss due to neurodegeneration that occurs mainly during aging. The accumulation of senescent cells has been related to aging. Furthermore, the expression of the variant ApoE ε4 is a critical risk factor for AD. Some events that occur in senescence, such as the secretion of pro-inflammatory molecules, and metabolic and epigenetic changes, in addition to the detection of ApoE4, may accelerate the progression of AD. Here, we discuss the implications of cellular senescence and the ApoE variants in AD. Molecular studies of these risk factors for AD may hence be pivotal to define new biomarkers and novel therapeutic strategies for this neurodegenerative pathology.