Affiliations: Department of Pathology & Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI, USA
Correspondence:
[*]
Correspondence to: Dr. Cara J. Westmark, Waisman Center for Developmental Disabilities, Room T507, 1500 Highland Avenue, Madison, Wisconsin 53705, USA. Tel.: +1 608 262 9730; E-mail: [email protected].
Note: [] Handling Associate Editor: Gary Arendash
Abstract: Amyloid-β protein precursor (AβPP) 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-β antibody. Our data strongly implicates AβPP or a catabolite in seizure susceptibility and suggests that mGluR5 mediates this response.
Keywords: Alzheimer's disease, amyloid-β, amyloid-β protein precursor, audiogenic seizure, Down syndrome, metabotropic glutamate receptor 5
