It has been unclear whether the presynaptic protein α-synuclein (α-syn) has a role in adult neurogenesis in the hippocampal dentate gyrus (DG). Here, mice in which the genes encoding α- and β-syn had been knocked out showed increased neurogenesis in the adult DG, but α-syn overexpression impaired newborn DG neuron survival and dendritic development. In patients with dementia with Lewy bodies, hippocampal α-syn levels were increased but the number of hippocampal cells expressing SOX2, a neural stem cell marker, declined. Together, these data suggest that α-syn is required for the development of new hippocampal neurons in adults.