Roberson Erik D, Scearce-Levie Kimberly, Palop Jorge J, Yan Fengrong, Cheng Irene H, Wu Tiffany, Gerstein Hilary, Yu Gui-Qiu, Mucke Lennart
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Science. 2007 May 4;316(5825):750-4. doi: 10.1126/science.1141736.
Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Abeta-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Abeta levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.
许多针对阿尔茨海默病的潜在治疗方法都以β淀粉样肽（Aβ）为靶点，人们普遍认为该肽会引发这种疾病。微管相关蛋白tau也与该病有关，但旨在针对tau的治疗方法能否阻止Aβ诱导的认知障碍尚不清楚。在此，我们发现降低内源性tau水平可预防表达人类淀粉样前体蛋白的转基因小鼠出现行为缺陷，而不会改变其较高的Aβ水平。降低tau水平还能保护转基因和非转基因小鼠免受兴奋性毒性作用。因此，降低tau水平可阻止Aβ和兴奋性毒素诱导的神经元功能障碍，可能是治疗阿尔茨海默病及相关病症的有效策略。
