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P4‐168: Mitochondrial dysfunction and neurodegeneration in P301L tau transgenic AIF‐deficient mice
Author(s) -
Kulic Luka,
Wollmer Marc Axel,
Rhein Virginie,
Pagani Lucia,
Kuehnle Katrin,
Cattepoel Susann,
Tracy Jay,
Eckert Anne,
Nitsch Roger M.
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.2008.05.2235
Subject(s) - neurodegeneration , oxidative stress , genetically modified mouse , mitochondrion , biology , tau protein , mitochondrial biogenesis , parkinsonism , tauopathy , dentate gyrus , alzheimer's disease , neuroscience , microbiology and biotechnology , endocrinology , transgene , medicine , hippocampus , genetics , disease , gene
locus in these two brain regions from 10 LOAD subjects and 10 agematched controls. DNA was prepared using techniques that enrich the sample for mtDNA and reduce in vitro DNA damage. The proportion of nuclear DNA was quantified for each sample to determine the [mtDNA] since variation in mtDNA copy number has been reported. Results: Initial results suggest increased mtDNA damage in the temporal cortex, as compared to the cerebellum, for both AD and control subjects (p 0.004). In the temporal cortex we observed a significant difference in mtDNA damage between AD and control subjects (p 0.0011) but not in the cerebellum (p 0.2799), We also found a significant reduction in the proportion of nuclear to mitochondrial DNA in AD as compared to control samples from the temporal cortex (p 0.001). Conclusions: These data indicate that mtDNA damage may be more severe in tissue affected by LOAD pathology and suggest an increase in mtDNA copy number in the temporal cortex. Investigation of additional subjects and mitochondrial loci is underway to confirm these findings.