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P1‐029: The Tg2576 mouse hippocampus shows early changes in the mitochondrial proteome that parallel those in models of other neurodegenerative diseases
Author(s) -
Jones Lesley,
Darko Turic,
Deschepper Mia,
Good Mark,
Owen Michael,
O'Donovan Michael,
Hoogendoorn Bastiaan
Publication year - 2008
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.2008.05.614
Subject(s) - proteome , hippocampal formation , hippocampus , genetically modified mouse , mitochondrion , phenotype , heat shock protein , biology , blot , wild type , transgene , endocrinology , medicine , microbiology and biotechnology , biochemistry , mutant , gene
Background: The Tg2576 mouse carries a human APP transgene with the Swedish mutation that gives rise to early onset Alzheimer’s disease (AD). The mice show Alzheimer’s like deficits in learning and memory from around 7-8 months and pathological deposition of amyloid from around 12 months. We were interested in changes in the protein complement of the hippocampus of these mice before and at early stages of phenotypic deficits compared with their wild-type littermates. Methods: We compared the hippocampal proteome of Tg2576 mice at 4 and 9 months of age with that of their wild-type littermates using Surface Enhanced Laser/Desorption Ionization mass spectrometry (Ciphergen) followed up by western blotting. Results: We detected changes in the quantities of several subunits of Complexes I, III and IV of the mitochondrial electron transport chain at 9 months of age. Increases were seen in some subunits and decreases in others. We also saw increased levels of haemoglobins A and B which could further imply that oxidative metabolism is compromised in the brains of the Tg2576 mice. When we examined the proteome of the Tg2576 hippocampus at 4 months we detected only three protein changes, one of which was an increase in the concentration of the mitochondrial heat shock protein 10. We see similar changes in mitochondrial proteins, including an increase in heat shock protein 10, in murine models of other neurodegenerative diseases. Conclusions: The first mitochondrial changes in the Tg2576 mice start much earlier than observed changes in phenotype or pathology implicating mitochondrial changes as an early event in the subsequent development of neurodegenerative pathology. This occurs in models of other neurodegenerative diseases implicating alterations in energy metabolism as a central pathological mechanism in neurodegeneration.