@SavaDx CRTX brilliantly explain both. Furthermore, over their lifetime, it turns out that some small percent of E4/E4 homozygotes do NOT get AD. Now we have a clear explanation- they must not have an active Pg infection secreting gingipains to point a finer point on this-- over 20+ years, 95% of all AD drugs have targeted amyloid and Tau or pTau. the thing is, APOE does not code for either amyloid or tau. it just doesn't make sense. Any valid scientific theory must account for known facts. but the other issue is that many people are not familiar with how infectious diseases actually spread. Pg is the keystone bacterium for gum disease. But studies indicate as many as 500 foreign pathogenic species present in gum disease. If you get ride of the ring-leader, those following along will not be able to do as much damage.