The fruit fly, Drosophila, is commonly used to study late-onset neurodegenerative diseases due to the combination of powerful genetic tools, cheap and simple husbandry and short lifespan. One widely-used measure of disease progression is the age-dependent decline in motor performance that manifests in most Drosophila neurodegeneration models. This is usually quantified using a simple climbing assay. However, the standard climbing assay lacks sensitivity and suffers from high variability meaning large numbers of flies are needed or bespoke apparatus and software solutions. Here, we present a modification of the open-source, MATLAB-based, DART software to measure the decline in “startle response” with age. We demonstrate that the DART setup is more sensitive to the motor performance decline induced by adult-onset neuronal expression of amyloid beta (Aβ) peptides than a traditional climbing assay despite using smaller cohorts of flies. DART also has the potential to generate multiple metrics of motor behaviour during the startle response. The software requires no coding skills to operate and the required apparatus can be purchased commercially. Therefore, DART is a more useful method than the climbing assay for longitudinal assays of motor performance and will enable higher-throughput screen for genetic and pharmacological modifiers of neurodegeneration. In our proof-of-concept screen for modifiers of Aβ-dependent phenotypes, we identified that in vivo knock-down of p53 in adult neurons is neuroprotective. This supports recent work targeting p53 in vitro and demonstrates the potential for DART to be used to screen for targets that ameliorate neurodegeneration.

在果蝇，果蝇，通常用来研究迟发性神经退行性疾病，由于强大的遗传工具，廉价和简单的饲养和寿命短的组合。一种广泛使用的衡量疾病进展的方法是在大多数果蝇中表现出年龄依赖性的运动表现下降神经退行性模型。通常使用简单的攀登分析来量化。但是，标准的爬升分析缺乏灵敏度，并且具有高可变性，这意味着需要大量苍蝇或定制设备和软件解决方案。在这里，我们对基于MATLAB的开源DART软件进行了修改，以测量“惊吓反应”随年龄的下降。我们证明，尽管使用了较小的蝇群，但DART设置对成人淀粉样β（Aβ）肽的成人发作神经元表达所引起的运动表现下降更为敏感，而不是传统的攀登实验。DART还可能在惊恐反应期间生成多种运动行为指标。该软件无需任何编码技能即可操作，所需的设备可以商业购买。因此，DART是比攀登分析更有效的方法，用于运动功能的纵向分析，并且可以对神经变性的遗传和药理修饰剂进行更高通量的筛选。在针对Aβ依赖型的修饰子的概念验证屏幕中，我们发现体内敲除成年神经元中的p53具有神经保护作用。这支持了近期针对p53的体外研究，并证明了DART用于筛选可改善神经变性的靶标的潜力。