Alzheimer's Genetics in the GWAS Era: A Continuing Story of 'Replications and Refutations'

After a decade of intensive investigation but only few replicable results, Alzheimer's disease (AD) genetics research is slowly picking up pace. This is mostly owing to the completion of several genome-wide association studies (GWAS), which have suggested the existence of over three dozen potential new AD susceptibility genes. Although only a handful of these could be confirmed in subsequent independent replication efforts to date, this success rate is still much higher than in the pre-GWAS era. This review provides a brief summary of the principal methodologic advances in genetics research of the past decade, followed by a description of the most compelling findings that these advances have unearthed in AD. The paper closes with a discussion of the persistent methodologic difficulties and challenges and an outlook on what we can expect to gain from the next 10 years of AD genetics research.