We will complete the characterization of the protective effects of neural progenitor cell (NPC) transplantation in E200K mice. We will also examine the effect of NPC transplantation on the progression of AD in 5xFAD mice, and we will characterize various pathological features of disease, rate of neurodegeneration and behavioral tests. These experiments may show for the first time whether it is possible to slow down neurodegeneration, particularly in models that are relevant to human AD. To compare the functional properties of NPSs from wild type vs. 5xFAD mice in vivo and in vitro, we will examine the response of resident adult NPCs to injury in vivo and compare that of 5xFAD to wild type mice. We will also compare the immune-modulatory and neuro-trophic properties of NPCs from 5xFAD and wild-type mice both in vitro (by co-culture and gene expression assays) and in vivo (by their effect of neurogenesis). These experiments will indicate whether NPCs from AD mice display defective functional properties. Finally, we will study the therapeutic functions of NPCs from human familial AD backgrounds compared with normal NPCs (to be provided by Dr. Noggle). We will examine human NPC properties using both in vitro and in vivo assays, as described above.