Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.
阿尔茨海默病（AD）是一种慢性中枢神经退行性疾病。AD 的主要病理特征为淀粉样蛋白 β 低聚物（AβOs）在胞外沉积形成老年斑，以及 tau 蛋白过度磷酸化在胞内积聚形成神经纤维缠结。本文提出了一种基于神经网络传感芯片的 AD 体外病理模型及其实时动态分析方法，在微电极阵列芯片上培养海马神经元并形成网络，使用 AβOs 诱导海马神经元构造 AD 体外模型，同时记录到锥体神经元和中间神经元两种放电模式，利用空间发放图谱和通道间的互相关系数验证了病理模型中神经元网络间信息连接的退化。该生物传感器能够从电信号上反应 AβOs 对神经网络的毒性反应以及神经元网络之间的信号传递功能，有望成为体外 AD 病理网络模型研究的一种新手段。.
Keywords: Alzheimer’s disease; hippocampal neuron; microelectrode array; neuronal network chip.