It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal
maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function
in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, synaptic activity,
neurogenesis and behavioral plasticity. Proteins involved in Wnt signaling have been found expressed in the adult
hippocampus suggesting that Wnt pathway plays a role in the hippocampal function through life. Indeed, Wnt ligands act
locally to regulate neurogenesis, neuronal cell shape and pre- and postsynaptic assembly, events that are thought to
underlie changes in synaptic function associated with long-term potentiation and with cognitive tasks such as learning and
memory. Recent data have demonstrated the increased expression of the Wnt antagonist Dickkopf-1 (DKK1) in brains of
Alzheimer´s disease (AD) patients suggesting that dysfunction of Wnt signaling could also contribute to AD pathology.
We review here evidence of Wnt-associated molecules expression linked to physiological and pathological hippocampal
functioning in the adult brain. The basic aspects of Wnt-related mechanisms underlying hippocampal plasticity as well as
evidence of how hippocampal dysfunction may rely on Wnt dysregulation is analyzed. This information would provide
some clues about the possible therapeutic targets for developing treatments for neurodegenerative diseases associated with
aberrant brain plasticity.