Polymorphism in the peroxisome proliferator-activated receptor α gene influences the risk for Alzheimer’s disease

The peroxisome proliferator-activated receptor α (PPAR-α) is a member of the steroid hormone super family of ligand-inducible transcription factors, involved in glucose and lipid metabolism. We screened for polymorphisms in the PPAR-α gene and detected two known polymorphisms located in exon 5 and intron 7. These polymorphisms were investigated for their possible association with Alzheimer’s disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism. The PPAR-α C → G polymorphism in exon 5 (L162V) was associated with AD, in that the V-allele was more frequent in AD patients than in healthy subjects. Further data analysis revealed that carriers of an PPAR-α L162V V-allele and an INS-1 allele presented with an increased risk for AD. Cerebrospinal fluid amyloid-β levels were influenced by PPAR-α L162V genotype. These results suggest, that PPAR-α polymorphism may be a risk factor for AD.