Cyclic-AMP response element-binding protein (CREB) signaling has a critical role 
in the formation of memories. CREB signaling is dysfunctional in the brains of 
mouse models of Alzheimer's disease (AD), and evidence suggests that CREB 
signaling may be disrupted in human AD brains as well. Here, we show that both 
CREB and its activated form pCREB-Ser(133) (pCREB) are reduced in the prefrontal 
cortex of AD patients. Similarly, the transcription cofactors CREB-binding 
protein (CBP) and p300 are reduced in the prefrontal cortex of AD patients, 
indicating additional dysfunction of CREB signaling in AD. Importantly, we show 
that pCREB expression is reduced in peripheral blood mononuclear cells (PBMC) of 
AD subjects. In addition, pCREB levels in PBMC positively correlated with pCREB 
expression in the postmortem brain of persons with AD. These results suggest 
that pCREB expression in PBMC may be indicative of its expression in the brain, 
and thus offers the intriguing possibility of pCREB as a biomarker of cognitive 
function and disease progression in AD.