Carro E, Trejo J L, Gerber A, Loetscher H, Torrado J, Metzger F, Torres-Aleman I
Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Avda. Dr. Arce 37, 28002 Madrid. Spain.
Neurobiol Aging. 2006 Sep;27(9):1250-7. doi: 10.1016/j.neurobiolaging.2005.06.015. Epub 2005 Sep 23.
Transgenic mice expressing mutant forms of both amyloid-beta (Abeta) precursor protein (APP) and presenilin (PS) 2 develop severe brain amyloidosis and cognitive deficits, two pathological hallmarks of Alzheimer's disease (AD). One-year-old APP/PS2 mice with high brain levels of Abeta and abundant Abeta plaques show disturbances in spatial learning and memory. Treatment of these deteriorated mice with a systemic slow-release formulation of insulin-like growth factor I (IGF-I) significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Abeta load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Abeta plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Abeta complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. Since levels of APP were not modified after IGF-I therapy, and in vitro data showed that IGF-I increases the transport of Abeta/carrier protein complexes through the choroid plexus barrier, it seems that IGF-I favors elimination of Abeta from the brain, supporting a therapeutic use of this growth factor in AD.
表达淀粉样β蛋白（Aβ）前体蛋白（APP）和早老素（PS）2突变形式的转基因小鼠会出现严重的脑淀粉样变性和认知缺陷，这是阿尔茨海默病（AD）的两个病理特征。一岁的APP/PS2小鼠脑内Aβ水平高且有大量Aβ斑块，表现出空间学习和记忆障碍。用胰岛素样生长因子I（IGF-I）的全身缓释制剂治疗这些病情恶化的小鼠，可显著改善类似AD的障碍。因此，IGF-I提高了认知能力，降低了脑内Aβ负荷，增加了突触蛋白水平，并减少了与Aβ斑块相关的星形胶质细胞增生。IGF-I的有益作用与与白蛋白、载脂蛋白J或甲状腺转运蛋白等蛋白质载体结合的脑内Aβ显著增加有关。由于IGF-I治疗后APP水平未改变，且体外数据表明IGF-I增加了Aβ/载体蛋白复合物通过脉络丛屏障的转运，似乎IGF-I有利于从脑中清除Aβ，支持将这种生长因子用于AD的治疗。
