Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Ageing Res Rev. 2014 Jan;13:13-37. doi: 10.1016/j.arr.2013.10.002. Epub 2013 Nov 21.
Alzheimer's disease (AD) is a widespread and devastating progressive neurodegenerative disease. Disease-modifying treatments remain beyond reach, and the etiology of the disease is uncertain. Animal model are essential for identifying disease mechanisms and developing effective therapeutic strategies. Research on AD is currently being carried out in rodent models. The most common transgenic mouse model mimics familial AD, which accounts for a small percentage of cases. The senescence-accelerated mouse prone 8 (SAMP8) strain is a spontaneous animal model of accelerated aging. Many studies indicate that SAMP8 mice harbor the behavioral and histopathological signatures of AD, namely AD-like cognitive and behavioral alterations, neuropathological phenotypes (neuron and dendrite spine loss, spongiosis, gliosis and cholinergic deficits in the forebrain), β-amyloid deposits resembling senile plaques, and aberrant hyperphosphorylation of Tau-like neurofibrillary tangles. SAMP8 mice are useful in the development of novel therapies, and many pharmacological agents and approaches are effective in SAMP8 mice. SAMP8 mice are considered a robust model for exploring the etiopathogenesis of sporadic AD and a plausible experimental model for developing preventative and therapeutic treatments for late-onset/age-related AD, which accounts for the vast majority of cases.
阿尔茨海默病(AD)是一种广泛存在且具有破坏性的进行性神经退行性疾病。目前,仍无法实现对疾病的根本性治疗,其病因也尚未明确。动物模型对于确定疾病机制和开发有效的治疗策略至关重要。AD 的研究目前正在啮齿动物模型中进行。最常见的转基因小鼠模型模拟家族性 AD,但其仅占病例的一小部分。衰老加速小鼠品系 8(SAMP8)是一种自发性加速老化动物模型。许多研究表明,SAMP8 小鼠具有 AD 的行为和组织病理学特征,即 AD 样认知和行为改变、神经病理学表型(前脑神经元和树突棘丢失、海绵状变性、神经胶质增生和胆碱能缺陷)、类似于老年斑的β-淀粉样蛋白沉积以及 Tau 样神经纤维缠结的异常过度磷酸化。SAMP8 小鼠可用于开发新的治疗方法,许多药理学制剂和方法对 SAMP8 小鼠有效。SAMP8 小鼠被认为是探索散发性 AD 病因发病机制的有力模型,也是开发针对大多数病例的迟发性/年龄相关性 AD 的预防和治疗方法的合理实验模型。