Molecular genetics of late-onset Alzheimer's disease

Late-onset Alzheimer's disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. Apolipoprotein E (APOE), especially the APOE* 4 allele, has been established as a strong susceptibility marker that accounts for nearly 30% of the risk in late-onset AD. However, as the APOE* 4 allele is neither necessary nor sufficient for the development of AD, it emphasizes the involvement of other genetic and/or environmental factors which, alone or in conjunction with APOE* 4, can modify the risk of AD. Recently, genome-wide linkage or linkage disequilibrium studies on late-onset AD have provided informative data for the existence of multiple putative genes for AD on several chromosomes, with the strongest evidence on chromosomes 12, 10, 9 and 6. This paper attempts to review the current progress on the identification of additional genetic loci for late-onset AD.