Abstract
Mounting evidence suggests that peroxisome proliferator-activated receptor-γ (PPAR-γ) is involved in the modulation of pathogenic events related to Alzheimer's disease (AD). Such events would include the cerebral deposition of amyloid-β (Aβ) and the consequent local inflammatory response. PPAR-γ has been shown to act on both fronts, reducing either the secretion of Aβ or the expression of pro-inflammatory cytokines. Recently, the relatively common Pro12Ala polymorphism in exon 2 of PPAR-γ has been associated with higher risk for late onset AD. Here, we compare the effect of PPAR-γ and its genetic variant on the secretion of Aβ. Our results indicate that, in neuronal cultured cells, the Pro12Ala substitution does not affect the anti-amyloidogenic capacity of PPAR-γ. Additional factors, PPAR-γ related, may therefore predispose aged subjects, carrying the Ala allele, to develop the neurodegenerative disease.
