Centre National De La Recherche Scientifique

The Buck Institute for Age Research

Buck Institute

Veronica Galvan

Dale E Bredesen

Patrick Mehlen

Filipe Calheiros-Lourenco

The invention provides methods and compositions for reducing or inhibiting net beta-amyloid peptide production and/or amyloid plaque formation. The methods and compositions involve administering a netrin-1 polypeptide or netrin-1 therapeutic to a subject in need thereof.

Compositions and methods for suppression of amyloid plaque formation associated with neurodegenerative disorders

In accordance with the present invention, it is demonstrated that selected mutations such as an Asp-&#x3e;Ala (D664A) mutation in APP (which prevents cleavage at the caspase cleavage site) prevent both hippocampal synaptic loss and dentate gyral atrophy, even though such mutations do not interfere with the production of A&#x3b2; or the formation of amyloid plaques in a transgenic model of Alzheimer's disease. Accordingly, in view of this finding, methods have been developed for the identification of agents which block cleavage at Asp664 of APP, including transgenic animals which are useful for such purpose, as well as methods for the use thereof for the treatment of neurodegenerative diseases.

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Novato, CA, United States of America

Veronica Galvan