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

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,...

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Autores principales: Bartolotti, N, Bennett, D A, Lazarov, O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995548/
https://www.ncbi.nlm.nih.gov/pubmed/27480489
http://dx.doi.org/10.1038/mp.2016.111
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author Bartolotti, N
Bennett, D A
Lazarov, O
author_facet Bartolotti, N
Bennett, D A
Lazarov, O
author_sort Bartolotti, N
collection PubMed
description 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.
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spelling pubmed-49955482016-09-07 Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells Bartolotti, N Bennett, D A Lazarov, O Mol Psychiatry Immediate Communication 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. Nature Publishing Group 2016-09 2016-08-02 /pmc/articles/PMC4995548/ /pubmed/27480489 http://dx.doi.org/10.1038/mp.2016.111 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Immediate Communication
Bartolotti, N
Bennett, D A
Lazarov, O
Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title_full Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title_fullStr Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title_full_unstemmed Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title_short Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
title_sort reduced pcreb in alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells
topic Immediate Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995548/
https://www.ncbi.nlm.nih.gov/pubmed/27480489
http://dx.doi.org/10.1038/mp.2016.111
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