Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of development including organogenesis, midbrain development as well as stem cell proliferation. Wnt signaling pathway plays different roles in the development of neuronal circuits and also in the adult brain, where it regulates synaptic transmission and plasticity. It has been also implicated in various diseases including cancer and neurodegenerative diseases, reflecting its relevance in fundamental biological processes. This review summarizes the progress about Wnts function in mature nervous system with a focus on Alzheimer's disease (AD). We discuss the prospects of modulating canonical and non-canonical Wnt signaling as a strategy for neuroprotection. This will include the potential of Wnts to: (i) act as potent regulators of hippocampal synapses and impact in learning and memory; (ii) regulate adult neurogenesis; and finally (iii) control AD pathogenesis.