Expression of the Neuronal Adaptor Protein X11alpha Protects Against Memory Dysfunction in a Transgenic Mouse Model of Alzheimer's Disease

Abstract

X11? is a neuronal-specific adaptor protein that binds to the amyloid-? protein precursor (A?PP). Overexpression of X11? reduces A? production but whether X11? also protects against A?-related memory dysfunction is not known. To test this possibility, we crossed X11? transgenic mice with A?PP-Tg2576 mice. A?PP-Tg2576 mice produce high levels of brain A? and develop age-related defects in memory function that correlate with increasing A? load. Overexpression of X11? alone had no detectable adverse effect upon behavior. However, X11? reduced brain A? levels and corrected spatial reference memory defects in aged X11?/A?PP double transgenics. Thus, X11? may be a therapeutic target for Alzheimer's disease.