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• W2065918069 abstract "The AddNeuroMed study aims to use pre-clinical and clinical studies to discover biomarkers for Alzheimer's disease (AD). In an attempt to improve the face validity of transgenic mouse models of AD and assist biomarke discovery and validation. Male and female B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mice (with the ‘Swedish’ mutation in amyloid precursor protein (APP) and the deletion of exon 9 in presenilin-1) and wild-type mice were fed either normal chow or pro-oxidant diet (low antioxidant, enhanced iron concentration) for three months from three months of age. Moreover, we hypothesise that a pro-oxidant diet will be associated with a greater pathological burden and alterations in normal synaptic biochemistry, perhaps more accurately reflecting the human AD pathology. We investigated expression levels of proteins associated both with AD pathology (including : APP, Presenilin, Insulin Degrading Enzyme and Complement Factor H), diet (including: glutathione), and markers of synaptic function, which have previously been shown to be altered in AD (including : synaptophysin, drebrin and vesicular glutamate transporter (VGLUT1)). Protein levels were analysed by SDS-PAGE and immunoblotting. Data were analysed by Univariate analysis with P<0.05 was taken to be statistically significant. N = 4 animals per group. Levels of insulin degrading enzyme were found to be significantly altered in by gender and the interaction between diet and genotype was also significant. Complement Factor H, previously shown in clinical AD samples to be differentially expressed was affected by interactions between gender and genotype but not diet (p=0.13). Glutathione (see also poster by Choudhry et al, this meeting) and synaptophysin levels were unaffected by diet, gender and transgene expression. Levels of drebrin (here used as a marker of post-synaptic glutamatergic synapses) were significantly different by gender and genotype, and further altered by interactions between gender and diet, diet and genotype and gender, diet and genotype. VGLUT1 expression was significantly altered by genotype alone. These data suggest a pertubation in glutamatergic signalling in those trangsenic mice receiving this pro-oxidant diet. Moreover, these data suggest this transgenic model may be of use in testing and validation of biomarkers." @default.
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• W2065918069 date "2008-07-01" @default.
• W2065918069 modified "2023-09-27" @default.
• W2065918069 title "P1-089: Biochemical characterization of the B6C3-Tg(APPswe,PSEN1dE9) 85Dbo/J mouse fed a pro-oxidant diet on behalf of the addneuromed group" @default.
• W2065918069 doi "https://doi.org/10.1016/j.jalz.2008.05.675" @default.
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