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P1‐062: Tau reduction prevents epileptiform activity in a mouse model of Alzheimer's disease: Gene expression microarray analysis
Author(s) -
Roberson Erik D.,
Meilandt William J.,
Yao Jinghua,
Yoo Jong,
Noebels Jeffrey L.,
Mucke Lennart
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.2008.05.648
Subject(s) - tau pathology , genetically modified mouse , transgene , medicine , neuroscience , gene expression , microarray analysis techniques , gene , premovement neuronal activity , microarray , microbiology and biotechnology , disease , pathology , biology , genetics , alzheimer's disease
2) as well as proteins involved in lysosomal degradation, such as cathepsin D. Proteasomal degradation is responsive to oxidative stress and cathepsin D is known to be involved in the apoptotic response to oxidative stress and aging, and its expression is increased in AD. We have also examined 14-3-3 , which has been shown to have a molecular chaperone role in the renaturation of aggregated proteins and is found in tangles in AD. Methods: As part of the AddNeuroMed project, mice were fed either normal chow or pro-oxidant diets (low antioxidant, enhanced iron concentration) for three months from three months of age. Protein levels have been analysed by SDS-PAGE and immunoblotting. Results: 14-3-3 levels were unaffected by diet, gender or the transgenes (p 0.05). 20S proteasome subunit 7 was affected by gender, with higher levels found in the females. Diet and genotype had no effect. Cathepsin D was not significantly affected by any of: diet, gender or genotype, but was affected by the combined effect of genotype and diet. In wild type mice cathepsin D levels were reduced when the pro-oxidant diet was provided, whereas in transgenics cathepsin D levels were increased in the presence of the pro-oxidant diet. Conclusions: These results indicate that protein degradation systems are differentially affected by gender, diet and genotype in this model of AD with enhanced oxidative stress through diet.