Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. During the progression, cognitive impairment extends to the domains of language, skilled movements, recognition and decision making. This research project are aimed at ultimately developing fast, innovative, and high throughput approaches for use in relevant biological model, as well as to utilize developing and existing technologies to break through the hurdles in Alzheimer’s disease research. To do so, systematic study of influences of beta-amylolid oligomers on cell dysfunction and death is prerequisite. We will study beta-amyloid oligomers-induced membrane perturbation and apoptosis. Thus, we will explore the relationship of cation dyshomeostasis and cell death using microfluidic devices and various spectroscopic techniques. Specifically, microfluidic devices, which can provide gradients of the substrates (i.e., oligomeric Aβs), will be employed to efficiently evaluate the effects of oligomeric Aβs on neurons under constant levels of Aβ oligomer in culture medium. For cellular effects, ‘cytosolic Ca2+ level’, ‘cell viability’, ‘mitochondrial activity’, and ‘cytochrome-c release’ will be monitored during cell culture. In addition, cyclosporine A and nerve growth factor will be tested to investigate their activities to reduce beta-amyloid-induced apoptosis.
Project end date: 08/18/11