title: Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bartolotti
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: O
authors.initials: O
authors.lastname: Lazarov
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000378:metabolism; D050882:CREB-Binding Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050880:p300-CBP Transcription Factors