In recent years, there was an increasing interest on candidate genes may play an important role in the development of Alzheimer's disease (AD). Several genome wide screens have undertaken so far or expanded recently, and suggested a number of genomic areas that may contain novel susceptibility genes for AD, in particular most compelling have been the findings on chromosome 12. Polymorphisms in different susceptibility genes on chromosome 12 (A2M, LRP1, CP2 and OLR1) are now being suggested as possible genetic markers for increased risk of developing AD. However, many of these studies are controversial and have shown conflicting results. Thus far, the search for the chromosome 12 Alzheimer's gene must continue and there are several other genes in this region that we are looking at. In this article, we focused on the current knowledge of the genetics of familial late-onset and sporadic AD linked to the chromosome 12, and the future search for other candidate genes.