Reduced pCREB in Alzheimer’s disease prefrontal cortex is reflected in peripheral blood mononuclear cells

• Published in: Molecular psychiatry Vol. 21; no. 9; pp. 1158 - 1166
• Main Authors: Bartolotti, N, Bennett, D A, Lazarov, O
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group
• Subjects: 631/337; 631/378; 692/53/2423; 82/29; Aged; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Alzheimer's disease; Autopsy; Behavioral Sciences; Biological Psychology; Biomarkers; Blood & organ donations; Brain; Brain - metabolism; Cognitive ability; CREB-Binding Protein - blood; CREB-Binding Protein - genetics; CREB-Binding Protein - metabolism; Dementia; Female; Humans; Immediate Communication; Leukocytes, Mononuclear - metabolism; Male; Medical research; Medicine; Medicine & Public Health; Middle Aged; Neurosciences; p300-CBP Transcription Factors - genetics; p300-CBP Transcription Factors - metabolism; Pathology; Pharmacotherapy; Phosphorylation; Prefrontal Cortex - metabolism; Proteins; Psychiatry; Signal Transduction; Transcription, Genetic; United States > US; Chicago Illinois
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2016.111

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.