Department of Pharmacology, University of Navarra, Pamplona, Spain.
Neurobiol Aging. 2013 Mar;34(3):805-8. doi: 10.1016/j.neurobiolaging.2012.06.005. Epub 2012 Jul 2.
The cannabinoid system seems to play an important role in various neurodegenerative diseases including Alzheimer's disease (AD). The relationship of cannabinoid receptors (CB(1)R and CB(2)R) to cognitive function and neuropathological markers in AD remains unclear. In the present study, postmortem cortical brain tissues (Brodmann area 10) from a cohort of neuropathologically confirmed AD patients and age-matched controls were used to measure CB(1)R and CB(2)R by immunoblotting. Correlational analyses were performed for the neurochemical and cognitive data. CB(1)R expression was significantly decreased in AD. Levels of CB(1)R correlated with hypophagia, but not with any AD molecular marker or cognitive status (Mini Mental State Examination score). The level of CB(2)R was significantly higher (40%) in AD. Increases in the expression of the glial marker glial fibrillar acidic protein were also found. CB(2)R expression did not correlate with cognitive status. Interestingly, expression levels of CB(2)R correlated with two relevant AD molecular markers, Aβ(42) levels and senile plaque score. These results may constitute the basis of CB(2)R-based therapies and/or diagnostic approaches.
大麻素系统似乎在包括阿尔茨海默病（AD）在内的各种神经退行性疾病中发挥重要作用。大麻素受体（CB1R 和 CB2R）与 AD 中的认知功能和神经病理学标志物的关系尚不清楚。在本研究中，使用队列的死后皮质脑组织（布罗德曼区 10）对神经病理学确诊的 AD 患者和年龄匹配的对照组进行免疫印迹，以测量 CB1R 和 CB2R。进行了神经化学和认知数据的相关分析。AD 中 CB1R 的表达显著降低。CB1R 水平与食欲减退相关，但与任何 AD 分子标志物或认知状态（迷你精神状态检查评分）无关。AD 中 CB2R 的水平显著升高（40％）。还发现神经胶质标志物神经胶质纤维酸性蛋白的表达增加。CB2R 的表达与认知状态无关。有趣的是，CB2R 的表达水平与两个相关的 AD 分子标志物 Aβ（42）水平和老年斑评分相关。这些结果可能构成基于 CB2R 的治疗和/或诊断方法的基础。
