APOE and Alzheimer disease: First off, although the pathological differences that occur in APOE4+ vs. APOE4− AD patients appear to center around tau pathology and the resulting brain atrophy, it is still quite possible that the earlier onset of Aß pathology that occurs in APOE4 carriers vs. non-carriers may play a direct role in the pathological differences that appear to occur in APOE4+ vs. APOE4− AD patients.