Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Neurobiol Aging. 2012 Feb;33(2):432.e1-432.e13. doi: 10.1016/j.neurobiolaging.2011.01.006. Epub 2011 Mar 2.
Cerebrovascular amyloidosis is caused by amyloid accumulation in walls of blood vessel walls leading to hemorrhagic stroke and cognitive impairment. Transforming growth factor-β1 (TGF-β1) expression levels correlate with the degree of cerebrovascular amyloid deposition in Alzheimer's disease (AD) and TGF-β1 immunoreactivity in such cases is increased along the cerebral blood vessels. Here we show that a nasally administered proteosome-based adjuvant activates macrophages and decreases vascular amyloid in TGF-β1 mice. Animals were nasally treated with a proteosome-based adjuvant on a weekly basis for 3 months beginning at age 13 months. Using magnetic resonance imaging (MRI) we found that while control animals showed a significant cerebrovascular pathology, proteosome-based adjuvant prevents further brain damage and prevents pathological changes in the blood-brain barrier. Using an object recognition test and Y-maze, we found significant improvement in cognition in the treated group. Our findings support the potential use of a macrophage immunomodulator as a novel approach to reduce cerebrovascular amyloid, prevent microhemorrhage, and improve cognition.
脑血管淀粉样变性是由血管壁中淀粉样物质的积累引起的，导致脑出血和认知障碍。转化生长因子-β1（TGF-β1）的表达水平与阿尔茨海默病（AD）中脑血管淀粉样沉积的程度相关，在这种情况下，TGF-β1 免疫反应沿脑血管增加。在这里，我们表明，鼻内给予蛋白酶体佐剂可激活巨噬细胞并减少 TGF-β1 小鼠中的血管淀粉样物质。动物从 13 个月大开始，每周接受一次蛋白酶体佐剂鼻内治疗，持续 3 个月。使用磁共振成像（MRI），我们发现尽管对照组动物表现出明显的脑血管病理学，但蛋白酶体佐剂可防止进一步的脑损伤，并防止血脑屏障的病理变化。使用物体识别测试和 Y 迷宫，我们发现治疗组的认知能力有显著提高。我们的发现支持使用巨噬细胞免疫调节剂作为减少脑血管淀粉样物质、预防微出血和改善认知的新方法的潜力。
