The insulin resistance and peripheral hyperinsulinemia have been known to promote the neurodegeneration in Alzheimer's disease (AD), such as beta amyloid (Abeta) deposits and increase of tau hyperphosphorylation. Therefore, correcting insulin dysregulation may offer a novel strategy for the treatment of AD. Pharmacologic treatment with thiazolidinedions, such as rosiglitazone and pioglitazone, agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), may offer some therapeutic relief of AD by lowering peripheral insulin and enhancing insulin sensitivity. In addition, PPARgamma agonists have been shown to inhibit inflammatory gene expression, alter Abeta homeostasis and exhibit neuroprotective effects. PPARgamma agonists represent a new and potentially efficacious treatment of AD.