Our present understanding of the genetic architecture of AD suggests that at least ten loci contribute to disease risk; APOE, CR1, CLU, PICALM, BIN1, EPHA1, MS4A, CD33, CD2AP and ABCA7. As described above, the contribution of APOE to predisposition to dementia in DS has been widely studied [38], but the influence of the other nine risk variants on the development of DAD has yet to be investigated. Here, CLU is linked to Alzheimer disease.