There is significant neuron cell loss in specific regions of the brain in Alzheimer's disease (AD) patients. Regeneration of these cells and circuits might restore lost cognitive function.Recent work has shown that new nerve cells are generated in the adult brain through a process known as neurogenesis. One therapeutic approach to advance this process is to transplant neural stem cells into the brain. Unfortunately, this approach has several major clinical development and delivery disadvantages and challenges.An alternative therapeutic strategy would be to use small orally bioavailable molecules that can promote proliferation of the existing neuronal stem cells in the brain.Dr. Brinton and colleagues have discovered that the neurosteroid allopregnenolone (AP ) furthers proliferation of stem cells in the rat brain.With ISOA funding, Dr. Brinton will test AP for its ability to induce proliferation of human neural stem cells and promote neurogenesis in a transgenic AD mouse model.A positive outcome of this program will lead to clinical development of AP or AP -like molecules for the treatment of AD, and create a breakthrough in the development of neurogenesis therapeutics.