The selective PPAR effects that we observed in mice are supported by human genomic data, suggesting a potential genomic link between PPARs and AD. Variations in PPARA and PPARG were modestly associated with withdrawal in humans while no evidence of association for either phenotype was demonstrated for variants in PPARD. PPARGC1A, which codes for PGC-1α, a coactivator for PPARγ transcriptional activity, was associated with AD. PGC-1α increases mitochondria (and peroxisome) generation while decreasing buildup of reactive oxygen species, allowing for positive effects of oxidative metabolism (Austin and St-Pierre, 2012). PGC-1α expression is highly inducible by physiological cues and decreased expression is associated with aging and other neurodegenerative diseases (Austin and St-Pierre, 2012) and schizophrenia (Jiang et al., 2013).
