Overexpression of the human beta-amyloid precursor protein downregulates cortistatin mRNA in PDAPP mice.

We measured preprocortistatin mRNA expression in young and aged transgenic (Tg) mice overexpressing the human beta-amyloid precursor protein (hbetaAPP) under the platelet-derived growth factor-beta promoter. Our findings suggest that the significant increase in hippocampal cortistatin mRNA expression during normal aging is significantly attenuated in Tg mice at an age known to exhibit beta-amyloid protein (Abeta) deposition. These deficits in cortistatin expression may play a role in the deficits in hippocampal-dependent spatial learning and sleep/wake states previously demonstrated in aged Tg mice.