The early-onset autosomal dominant Alzheimer’s diseases (AD) are caused by the inheritance of one of at least three different gene mutations and account for less than 5% of the prevalence. The most common form of the AD probably accounting for 50 to 75% of cases is late-onset disease associated with the inheritance of various apolipoprotein E (APOE) genotypes. The original report of the genetic association of APOE4 and Alzheimer’s disease contained photomicrographs that confirmed an earlier report of apoE immunostaining of plaques and tangles. It is dangerous to speculate on the future of AD research, especially with new surprising genetic mechanisms, such as trinucleotide repeats and genomic duplications, arising each year. The rapid confirmation of the genetic association of APOE alleles with the distribution of age of AD expression have energized and diversified the field. Protagonists of either amyloid deposition theories or tau/neurofibrillary tangle hypotheses are attempting to reconcile their theories with a role for apoE.