Hippocampal neurodegeneration occurs in most forms of dementia, including Alzheimer's disease. There is, therefore, intense interest in unravelling the mechanisms that underlie adult neurogenesis in this region of the brain. Now, on p. 4351, Steven Kernie and colleagues report that the cholesterol carrier apolipoprotein E (ApoE) is required for the maintenance of the neural stem/progenitor cell pool in the adult dentate gyrus region of the mouse hippocampus. The researchers show that ApoE is minimally expressed within the neural progenitor pool during early dentate gyrus development, when neural stem/progenitor cells are rapidly proliferating and differentiating into neurons. However, ApoE expression is markedly upregulated in adult dentate gyrus stem/progenitor cells, which proliferate more slowly. Notably, in ApoE-deficient mice, dentate gyrus neural stem/progenitor cells continue to proliferate rapidly, which ultimately depletes the neural stem cell pool. These and other data suggest that ApoE helps to regulate hippocampal progenitor cell fate and provide a mechanism by which human APOE polymorphisms might contribute to late-onset hippocampal neurodegenerative diseases.