Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Alzheimer's Disease Research Center, Karolinska Institutet, Stockholm, Sweden.
J Alzheimers Dis. 2010;22(3):829-38. doi: 10.3233/JAD-2010-100663.
The present work investigated the involvement of cortisol and its receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), in Alzheimer's disease (AD). Cortisol was measured in cerebrospinal fluid (CSF) samples from controls, mild cognitive impairment (MCI), progressive MCI evolving to AD, and AD. CSF cortisol levels do not seem to have a prognostic value, as increases in cortisol levels were found only in AD patients. GR expression was decreased while MR expression was increased in the frontal cortex of AD. When considering degeneration (ratio to synaptophysin and the post-synaptic marker PSD95), GR expression was similar between controls and AD, suggesting that GR loss was due to synaptic degeneration in AD. Increases in cortisol levels and MR expression were associated to an apolipoprotein E4 genotype. Cognitive status was negatively associated to CSF cortisol. In apolipoprotein E4 carriers, MR but not GR expression, negatively correlated to Mini-Mental Status Examination score and positively correlated to frontal cortex amyloid-β levels. It is concluded that there is a dysregulation of the hypothalamus-pituitary-adrenal axis in AD that seems to be consequence rather than cause of AD.
本研究调查了皮质醇及其受体，即糖皮质激素受体（GR）和盐皮质激素受体（MR），在阿尔茨海默病（AD）中的作用。我们检测了对照组、轻度认知障碍（MCI）、进展性 MCI 发展为 AD 以及 AD 患者的脑脊液（CSF）样本中的皮质醇水平。CSF 皮质醇水平似乎没有预后价值，因为只有 AD 患者的皮质醇水平升高。AD 患者的额叶皮质中 GR 表达降低，而 MR 表达增加。当考虑到（与突触小泡蛋白和突触后标志物 PSD95 的比值）退化时，GR 表达在对照组和 AD 之间相似，表明 GR 丢失是由于 AD 中的突触退化。皮质醇水平升高和 MR 表达增加与载脂蛋白 E4 基因型有关。认知状态与 CSF 皮质醇呈负相关。在载脂蛋白 E4 携带者中，MR 而不是 GR 表达与简易精神状态检查评分呈负相关，与额叶皮质淀粉样蛋白-β水平呈正相关。研究结论认为，AD 患者的下丘脑-垂体-肾上腺轴失调似乎是 AD 的结果而不是原因。
