Modeling Alzheimer's disease on-chip using microfluidic and tissue engineering approaches

阿尔茨海默病(AD)是一种进行性神经退行性疾病，与大脑的认知功能障碍有关。据估计，加拿大有50万人患有阿尔茨海默病，其中包括7万名65岁的老人。阿尔茨海默病的主要病因尚未明确发现，因此，阻止该病或逆转其进展的有效治疗方法尚未确立。人们主要认为淀粉样β蛋白(A-β)等一组可溶性折叠蛋白在大脑中聚集成不溶的形式，在神经元变性功能中发挥重要作用。AD患者中的β可通过直接沉积在突触上而在细胞外或细胞内通过阻断轴突传递而损害突触功能。现有的模型不能确定这两种方式中的任何一种在突触功能障碍中的作用，因为无法将分子局部递送到特定的细胞室。特别是微流控技术，具有将分子时空输送到突触部位的能力。拟议工作的总体目标是了解时空递送到突触的细胞外Aβ多肽是如何贡献的

Alzheimer's Disease (AD) is a progressive neurodegenerative disease associated with cognitive dysfunction in the brain. An estimated 500,000 Canadian have AD, including 70,000 age <65 years. The main cause of AD has not been clearly discovered, and therefore the effective treatment to stop the disease or reverse its progression has not yet been established. It is mainly believed that a group of soluble folded proteins like Amyloid beta (Aβ) aggregates to insoluble forms in the brain where they play an essential role in neuronal degeneration functions. Aβ in AD patients can impair synaptic function extracellularly via the direct deposition on synapses or intracellularly through interrupting the axonal transmission. The existing models are not able to determine the contribution of any of these two ways in synaptic dysfunction due to inability in local delivery of molecules into specific cellular compartments. Microfluidics, in particular, has the capability for spatiotemporal delivery of molecules to the synaptic site. The overall objective of the proposed work is to understand how extracellular Aβ peptides spatiotemporally delivered to synapses contribute