The principal findings of this study are that genetic variation in PICALM, BIN1, CD2AP and RIN3, four genes suggested to be involved in blood–brain barrier amyloid-β transcytosis, are associated with increased risk of Alzheimer’s disease, all dementia, and suggested vascular dementia in the general population independent of the strong APOE genotype. The gene discussed is PICALM; the disease is Alzheimer disease.