2012 Theses Doctoral

Modeling Alzheimer's Disease Using Cellular Reprogramming Technologies

Chau, Lily

Two cellular reprogramming technologies have emerged that demonstrate that cell-fate can be converted by ectopic expression of defined transcription factors: induced pluripotent stem (iPS) cell technology and induced neuronal (iN) cell technology. These recent advances in cell reprogramming strategies have great potential utility for patient-specific disease modeling and for applications in regenerative medicine. Current models of neurodegenerative diseases are limited in their representation of disease phenotypes and there is an essential need for human cellular models of neurodegenerative disorders. Induced pluripotent stem (iPS) cell technology offers a two-step approach to disease modeling, in which patient somatic cells are first reprogrammed to a pluripotent state and subsequently differentiated in neurons. In contrast, induced neuronal (iN) cell technology allows for the direct conversion of somatic cells to neurons. Here I demonstrate the modeling of Alzheimer's disease (AD) using both iPS and iN cellular reprogramming technologies. These bioengineered human cell-based models of AD provide unique and invaluable tools for elucidating the mechanism of AD pathogenesis.