Alzheimer's Disease and Down Syndrome Rodent Models Exhibit Audiogenic Seizures

Amyloid-beta protein precursor (A beta PP) is overexpressed in Alzheimer's disease (AD), Down syndrome (DS), autism, and fragile X syndrome. Seizures are a common phenotype in all of these neurological disorders, yet the underlying molecular mechanism(s) of seizure induction and propagation remain largely unknown. We demonstrate that AD(Tg2576) and DS (Ts65Dn) mice exhibit audiogenic seizures, which can be attenuated with antagonists to metabotropic glutamate receptor 5 (mGluR5) or by passive immunization with anti-amyloid-beta antibody. Our data strongly implicates A beta PP or a catabolite in seizure susceptibility and suggests that mGluR(5) mediates this response.