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. This evidence concerns the gene PICALM and early-onset autosomal dominant Alzheimer disease.