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

Department of Pathology & Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 3.61). 04/2010; 20(4):1009-13. DOI: 10.3233/JAD-2010-100087
Source: PubMed

ABSTRACT Amyloid-beta protein precursor (AbetaPP) 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 AbetaPP or a catabolite in seizure susceptibility and suggests that mGluR5 mediates this response.

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