Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells.
Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells.
复制标题
DOI：
10.1038/mp.2016.111
复制
发表时间：
2016-09
影响因子：
11
通讯作者：
Lazarov O
中科院分区：
文献类型：
--
作者：
Bartolotti N;Bennett DA;Lazarov O
环磷酸腺苷反应元件结合蛋白（CREB）信号在记忆的形成中起着关键作用。CREB信号在阿尔茨海默病（AD）小鼠模型的大脑中功能失调，有证据表明CREB信号在人类AD大脑中也可能被破坏。在这里，我们表明，CREB和它的激活形式pCREB-Ser 133（pCREB）减少在AD患者的前额叶皮层。类似地，转录辅因子CREB结合蛋白（CBP）和p300在AD患者的前额叶皮层中减少，表明AD中CREB信号传导的额外功能障碍。重要的是，我们表明，pCREB的表达减少，在外周血单核细胞（PBMC）的AD受试者。此外，PBMC中的pCREB水平与AD患者死后脑中的pCREB表达呈正相关。这些结果表明，pCREB在PBMC中的表达可能是其在脑中表达的指示，因此提供了pCREB作为AD中认知功能和疾病进展的生物标志物的有趣的可能性。
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-Ser133 (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.