Woodruff-Pak Diana S
Department of Psychology, Temple University, Philadelphia, PA 19122, USA.
J Alzheimers Dis. 2008 Dec;15(4):507-21. doi: 10.3233/jad-2008-15401.
This Special Issue of the Journal of Alzheimer's Disease (JAD) provides an overview of animal models of Alzheimer's disease (AD). Very few species spontaneously develop the cognitive, behavioral, and neuropathological symptoms of AD, yet AD research must progress at a more rapid pace than the rate of human aging. In recent years, a variety of models have been created--from tiny invertebrates with life spans measurable in months to huge mammals that live several decades. The fruit fly, Drosophila melanogaster, is a powerful genetic tool that has recently emerged as a model of AD with neural features and assessable learning and memory. Transgenic mice are the most widely used animal models of AD and have yielded significant research breakthroughs. Accelerated aging seen in the SAMP8 mouse is a non-transgenic model with great utility. Rat models provided early evidence about the deleterious impact of amyloid-beta (Abeta) on neurons and continue to provide insights. Rabbits, as langomorphs, are more closely related to primates than are rodents and have conserved the sequence of Abeta in humans (as have canines and non-human primates). The hypercholesterolemic rabbit is an excellent AD model. The aging canine develops AD neuropathology spontaneously and is especially suitable for tests of therapeutics. Non-human primates are invaluable for the development of therapeutics translating to humans. Each animal model has limitations and strengths, but used together in complementary fashion, animal models for research on AD are essential for rapid progress toward a cure.
《阿尔茨海默病杂志》(JAD)的这一特刊概述了阿尔茨海默病(AD)的动物模型。很少有物种会自发出现AD的认知、行为和神经病理学症状,但AD研究的进展速度必须快于人类衰老的速度。近年来,已经创建了多种模型——从寿命以月计算的小型无脊椎动物到寿命长达数十年的大型哺乳动物。果蝇,即黑腹果蝇,是一种强大的遗传工具,最近已成为具有神经特征且可评估学习和记忆能力的AD模型。转基因小鼠是使用最广泛的AD动物模型,并取得了重大研究突破。SAMP8小鼠中出现的加速衰老现象是一种具有很大实用价值的非转基因模型。大鼠模型为β淀粉样蛋白(Aβ)对神经元的有害影响提供了早期证据,并继续提供相关见解。兔子作为兔形目动物,与灵长类动物的关系比啮齿动物更密切,并且保留了人类Aβ的序列(犬类和非人类灵长类动物也是如此)。高胆固醇血症兔子是一种优秀的AD模型。衰老的犬类会自发出现AD神经病理学症状,特别适合用于治疗测试。非人类灵长类动物对于开发可转化至人类的治疗方法具有不可估量的价值。每种动物模型都有其局限性和优势,但以互补的方式共同使用时,AD研究的动物模型对于实现治愈的快速进展至关重要。