Pyk2-based gene therapy gene therapy attenuates cognitive deficits associated to alzheimer's disease

In the present invention it is shown that the inactivation of the Pyk2 gene does not alter hippocampal development but prevents hippocampal-dependent memory tasks and LTP. Inventors clearly provide evidence for multiple roles of Pyk2 in spine morphology and post synaptic structure. Thus, the inventors used direct overexpression of PYK2 by AAV-mediated gene transfer into the brain of Alzheimer’s mouse models and found that overexpression of PYK2 in this models improves synaptic properties and spine density deficits wich is also accompanied by a rescue of spatial memory. Accordingly it was demonstrated that PYK2 may restore cognitive functions in neurodegenerative diseases. Thus the present invention relates to methods and pharmaceutical compositions for the treatment of neurodegenerative disease. In particular the present invention relates to a method of treating neurodegenerative disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid molecule encoding for PYK2 polypeptide.