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P1‐065: Oxidative load regulates amyloid burden in vitro and in vivo in an APP X PS1 transgenic mouse model of Alzheimer's disease
Author(s) -
Choudhry Fahd,
Francis Paul T.,
Howlett David R.,
Richardson Jill R.C.,
Williams Robert J.
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.2008.05.651
Subject(s) - oxidative stress , in vivo , senile plaques , genetically modified mouse , glutathione , transgene , amyloid precursor protein , antioxidant , amyloid (mycology) , chemistry , medicine , endocrinology , alzheimer's disease , pathology , biology , biochemistry , disease , genetics , gene , enzyme
widespread throughout different cortical areas and the hippocampal formation (CA1, CA2, CA3 and dentate gyrus). In the neocortex, the intracellular A is most notable in pyramidal neurons of lamina 5, but ubiquitously found in all layers from lamina 2 to 6. Intracellular A accumulation progressively increases with aging, leading to the formation of extracellular A amyloid plaques by 9 to 11 months of age. Amyloid plaque deposition starts in the hippocampus, spreading later to neoand parietal cortex areas, entorhinal cortex and even thalamus. Preliminary results reveal an upregulation of ERK1/2 phosphorylation when compared to non-transgenic littermates rats, which coincides with the phase of intracellular A accumulation. The behavioural phenotype characterization is being completed, paying particular attention to the effect of intracellular A and extracellular plaque deposition stages on learning and memory acquisition. Also, the phosphorylation pattern of ERK1/2 and CREB proteins are currently being studied during the initial learning phase of the Morris water maze task. Conclusions: These investigations demonstrated that transgenic rats can be effective models to investigate Abeta-induced Alzheimer’s like pathology. This model should have some advantage over mice models since rats behaviour is richer and their brain size is more suitable for in vivo studies.