Whereas Cdk5 activity was aberrantly upregulated in APP/PS1 mouse hippocampi, pioglitazone administration in APP/PS1 mutant mice for 7 consecutive days significantly reduced Cdk5 activity to normal level (Fig 3G & 3H), confirming that the anti-diabetes drug pioglitazone can suppress Cdk5 hyper-activation in AD mouse models by reducing p35 level. Here, CDK5 is linked to diabetes mellitus.