A crucial limitation to our understanding of Alzheimer's disease (AD) is the inability to test hypotheses on live, patient-specific neurons. Patient autopsies are limited in supply and only reveal endpoints of disease. Rodent models harboring familial AD mutations lack important pathologies, and animal models have not been useful in modeling the sporadic form of AD because of complex genetics. The recent development of induced pluripotent stem cells (iPSCs) provides a method to create live, patient-specific models of disease and to investigate disease phenotypes in vitro. A proper understanding of the initiating events of AD and the existence of live disease models that accurately recapitulate the pathogenesis would lead to a much better informed therapeutic development effort.
Scientists at UC San Diego have developed the first true human neuronal model for hereditary and sporadic Alzheimer's disease. Specifically, human induced pluripotent stem cells made from Alzheimer's disease patients are sequentially converted into neural stem cells and ultimately neurons. The resultant human neurons are quantified with respect to key behaviors (e.g. proteolytic processing of amyloid precursor protein, phosphorylation of the tau protein, activation of GSK3 kinase). Additionally, the cells are also suitable for measuring synaptic phenotype, autophagy and other disease behaviors. This technology may be used diagnostically to predict the development of sporadic Alzheimer’s disease and allows drugs for Alzheimer's disease to be tested using human materials.
A patent has been filed on this technology. U.S. patent rights are available for commercialization. Detailed information is available under a secrecy agreement.