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P1–007: Alterations in metabotropic and ionotropic glutamate receptor expression in the APP V717F transgenic mouse model of Alzheimer's disease
Author(s) -
Kingston Ann E.,
Gillard Samantha E.,
Day Theresa A.,
Casley Christopher,
Lakics Viktor,
O'Neill Michael J.,
Bales Kelly R.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.382
Subject(s) - glutamate receptor , ionotropic effect , receptor , metabotropic glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 8 , receptor expression , endocrinology , medicine , biology , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , genetically modified mouse , metabotropic glutamate receptor 6 , hippocampal formation , glutamatergic , transgene , biochemistry , gene
accompanied with memory impairment followed by global cognitive deficits. Accumulation of beta-amyloid peptide 42 (A 42) in the brain is widely believed to be central etiology of AD. However, the precise molecular mechanisms underlying neuronal injury and death caused by A 42 remain to be elucidated. In vitro, A 42 can form a wide array of structures, including multiple monomer conformers, various size of oligomers, A derived diffusible ligands (ADDLs), protofibrils, fibrils and spheroids. Recent research efforts have been focused on understating the relationship between these different misfolding structures and neurotoxicity and the relevance to AD pathogenesis. In previous work, we have reported that the transgenic flies expressing A 42 fused to secretion signal in neurons showed progressive amyloid deposits formation, learning defects and neurodegeneration. Our recent study using immuno-electron microscopy further confirmed that most of A 42 accumulation occurred intraneuronally. These results indicate our A 42 fly is a useful model system to study intraneuronal toxicity of A 42 in vivo.