Alzheimer's disease (AD) shares Pathophysiological features with type 2 diabetes (T2D). The nuclear receptor peroxisome Proliferator- activated receptor GAMMA (PPARγ) is a ligand- activated transcription factor that regulates glucose and lipid metabolism and suppress inflammatory gene expression.

The potential therapeutic role of PPARγ on cognitive impairment and visuospatial memory in insulin resistance-induced AD using Pioglitazone; a PPARγ agonist.

AD was induced in 6 weeks old male rats by adding 6mg/L copper sulphate to drinking water for 8 weeks. Rats were randomly divided into 4 groups(n=10). (1) Normal control group on plain water, (2) AD control group, (3) Fructose drinking induced insulin resistance (IR) AD group, (4) Pioglitazone-treated group received orally (10mg/kg/day) at a volume of 2 ml/kg/day for the last 12 weeks of the 16 weeks period. Groups (3),(4) received 10% fructose solution in drinking water for 16 weeks after developing AD. Cognitive functions were assessed using discrimination index (DI) in object recognition test (ORT) and escape latency in Morris water maze(MWM) test. PPARγ was investigated for its role on γ-secretase and α secretes as well as glucose homeostasis.

PPARγ level was significantly elevated in IR-induced rats. However, Pioglitazone treatment was associated with restoration of PPARγ level to approximately normal values. Moreover, IR produced significant reduction in DI and prolongation of escape latency. Activation of PPARγ through Pioglitazone showed significant improvement in IR-induced dysfunctions in cognitive function and visuospatial memory in ORT and MWM tasks.

PPARγ agonists have a therapeutic potential in AD