An overall similar approach recently showed that SNPs of FKBP5 were associated with alcohol withdrawal in humans, and Fkbp5 knockout mice also showed greater withdrawal severity (Huang et al., 2014). Our results provide support for the first human genetic link between PPARs and alcohol-related phenotypes and suggest that further studies are warranted to evaluate repurposing PPAR agonists for treating AD. Some of these drugs are already FDA approved and some have been nominated for treating addictions in preclinical studies. The study by Mason et al. (2014) provides an example of a clinical trial showing the potential of repurposing gabapentin, a widely prescribed calcium channel/GABA medication, for treating AD. Clinical studies showing favorable drug safety profiles and effectiveness in treating AD and relapse-dependent symptoms will benefit pharmacotherapies and offer patients more treatment options. We propose that behavioral evaluation of drug targets in animals, followed by analysis of genetic variants in humans, may be an effective strategy for advancing therapeutics for AD and other polygenic diseases.
