Department of Anesthesiology, University of Illinois, Chicago, IL, USA.
Neurobiol Aging. 2013 Oct;34(10):2361-9. doi: 10.1016/j.neurobiolaging.2013.03.023. Epub 2013 Apr 18.
The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer's disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, and compared that with changes in NA levels and astrocyte activation. Total amyloid beta (Aβ)40 and Aβ42 levels were increased in the aged group, as were numbers of amyloid plaques detected using antibody 6E10. Low levels of Aβ42 were detected in 1 of 5 younger animals, although diffusely stained plaques were observed in 4 of these. Increased glial fibrillary acidic protein staining and messenger RNA levels were significantly correlated with increased age, as were cortical NA levels. Levels of Aβ42 and Aβ40, and the number of 6E10-positive plaques, were correlated with NA levels. Interestingly messenger RNA levels of glial derived neurotrophic factor, important for noradrenergic neuronal survival, were reduced with age. These findings suggest that amyloid pathology in aged vervets is associated with astrocyte activation and higher NA levels.
豚尾猴是一种旧大陆猴,越来越多地被用作人类疾病的模型。除了斑块和缠结外,阿尔茨海默病的另一个标志是合成去甲肾上腺素(NA)的神经元受损。我们描述了年轻和老年豚尾猴后颞叶的淀粉样蛋白负担,并将其与 NA 水平和星形胶质细胞激活的变化进行了比较。老年组的总β淀粉样蛋白(Aβ)40 和 Aβ42 水平增加,使用抗体 6E10 检测到的淀粉样斑块数量也增加。尽管在其中 4 只动物中观察到弥散染色的斑块,但在 5 只年轻动物中有 1 只检测到 Aβ42 水平较低。胶质纤维酸性蛋白染色和信使 RNA 水平的增加与年龄的增加显著相关,皮质 NA 水平也是如此。Aβ42 和 Aβ40 的水平以及 6E10 阳性斑块的数量与 NA 水平相关。有趣的是,对于去甲肾上腺素能神经元存活很重要的神经胶质衍生神经营养因子的信使 RNA 水平随着年龄的增长而降低。这些发现表明,老年豚尾猴的淀粉样蛋白病理学与星形胶质细胞激活和更高的 NA 水平有关。