CDKN1A and Alzheimer disease: Although the observations made in FAD lymphocytes may not exactly reflect the changes occurring in FAD brains, the fact that p21 levels change in response to both mitogenic stimuli and cellular stressors, may offer an explanation for the relationship between cellular stress and unscheduled cell cycle entry observed in susceptible AD neurons in agreement with the “two-hit” hypothesis [12, 72, 73].