While we have understood the bases for mendelian, early-onset Alzheimer disease for nearly 2 decades,1 elucidation of the genetic risks for late-onset disease beyond the apolipoprotein E locus, discovered in 1993,2 had been painfully slow until the last year. From 1993 to 2009, thousands of genetic association studies on Alzheimer disease had been published without any becoming generally accepted as true risk loci for the disease.3 With the benefit of hindsight, we now have some indication of why no other risk loci were found during this period; simply, there are no other loci with similar effect sizes to apolipoprotein E to be found.4 Now, however, with the advent of whole-genome associations, we are beginning to find the weaker risk loci for the disease.
Hardy J, Williams J. Identification of Alzheimer Risk Factors Through Whole-Genome Analysis. Arch Neurol. 2010;67(6):663–664. doi:10.1001/archneurol.2010.97