It is likely that progress in therapeutic approaches against Alzheimer’s disease is prevented by a lack in our understanding of how Aβ and p-tau interact to trigger the disease.2 In a previous paper, we showed that the major subset of principal neurons in alEC LII, unique in their expression of reelin, are prone to accumulate iAβ.38 Our current data show that long before Aβ-plaques start to form, reelin and iAβ42 can structurally associate in these neurons. The gene discussed is RELN; the disease is Alzheimer disease.