Recent evidence supports a role of the Wnt pathway in neurodegenerative disorders such as Alzheimer's disease (AD). A relationship between amyloid‐β‐peptide (Aβ)‐induced neurotoxicity and a decrease in the cytoplasmatic levels of β‐catenin has been proposed. Also, the inhibition of glycogen synthase kinase (GSK‐3β), a central modulator of the pathway, protects rat hippocampal neurons from Aβ‐induced damage. Interestingly, during the progression of AD, it has been described that active GSK‐3β is found in neuronal cell bodies and neurites, co‐localizing with pre‐neurofibrillary tangles observed in disease brains. Since Aβ oligomers are associated with the post‐synaptic region and we have found that the non‐canonical Wnt signaling modulates PSD‐95 and glutamate receptors, we propose that the synaptic target for Aβ oligomers in AD is the postsynaptic region and at the molecular level is the non‐canonical Wnt signaling pathway. Altogether, our evidence suggests that a sustained loss of Wnt signaling function may be involved in the Aβ‐dependent neurodegeneration observed in AD brains and that the activation of this signaling pathway could be of therapeutic interest in AD.