Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease

Alzheimer's disease is characterized by progressive memory loss and cognitive decline. The hippocampal formation is the most vulnerable brain area in Alzheimer's disease. Neurons in layer II of the entorhinal cortex and the CA1 region of the hippocampus are lost at early stages of the disease. A unique feature of the hippocampus is the formation of new neurons that incorporate in the dentate gyrus of the hippocampus. New neurons form synapses with neurons in layer II of the entorhinal cortex and with the CA3 region. Immature and new neurons are characterized by high level of plasticity. They play important roles in learning and memory. Hippocampal neurogenesis is impaired early in mouse models of Alzheimer's disease and in human patients. In fact, neurogenesis is compromised in mild cognitive impairment (MCI), suggesting that rescuing neurogenesis may restore hippocampal plasticity and attenuate neuronal vulnerability and memory loss. This review will discuss the current understanding of therapies that target neurogenesis or modulate it, for the treatment of Alzheimer's disease.