Mechanical Properties of Microglia: Role in Alzheimer's Disease?

Alzheimer ’s disease (AD) currently affects an estimated 4.5 million Americans. This number is predicted to more than double in the next fifty years. AD is a disorder of the elderly brain which impairs thinking, memory, and behavior, and ultimately leading to death. According to the Alzheimer’s Association and the National Institute on Aging, the annual cost of caring for individuals with AD is at least $100 billion.

Microglia are cells within the central nervous system whose role is to migrate to the site of brain injury and phagocytose tissue debris. There is an on going debate regarding the role of microglia in AD. Studies have shown the congregation of activated microglia around amyloid plaques which are characteristic of the AD brain. This leads some to believe that the migration of activated microglia to amyloid deposits creates increased concentrations of neurotoxins which damage neurons, and ultimately causes AD. Conversely, some theorize that microglia dysfunction and death is a result of AD. More specifically, they believe that as microglia near senescence they are unable to adequately support the neural network so neurodegeneration occurs. Therefore, amyloid plaques are a symptom of AD rather than its cause.

The migratory ability of microglia is a function of their ability to alter their shape. Therefore, characterizing their deformability will provide valuable information regarding their behavior and their role in AD.

Currently, micropipette aspiration is the standard technique for measuring cell deformability. However, it is difficult to use and can only evaluate one cell at a time, making it very time-consuming. Therefore, an automated microfluidic device that can measure the deformability of various cells simultaneously will be of significant benefit. The goal of this project is to design such a device, and then to characterize the deformability of aging microglia in an effort to better understand their role in AD.