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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-8-15
pubmed:abstractText
We have previously demonstrated in a transgenic rat model of tauopathy that human misfolded truncated tau derived from Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo. We employed this model to investigate the impact of truncated tau expression levels on life span, neuronal loss and the final load of neurofibrillary tangles (NFTs) in transgenic rats. Two independent transgenic lines (SHR72, SHR318), that display different expression levels of truncated tau, were utilized in this study. We found that transgene expression levels in the brain of SHR72 rats were 44% higher than in SHR318 rats and that truncated tau protein levels determined the survival rate of transgenic rats. The line with higher expression levels of truncated tau (SHR72) showed decreased median survival (222.5 days) when compared with the line with lower expression (SHR318; 294.5 days). Interestingly, NFT loads (total NFT/total neurons) were very similar in terminal stages of disease in both transgenic lines (SHR72 - 10.9%; SHR318 - 11.6%), despite significantly different expression levels of truncated tau. Moreover, mean neuron numbers in the hippocampus (CA1-3) and brain stem (gigantocellular reticular nucleus) in the two transgenic rat strains in the terminal stages of disease were similar, and did not differ significantly from those observed in age-matched non-transgenic controls. These findings suggest that the expression levels of misfolded truncated tau determine the life span in a transgenic rat model of tauopathy without causing neuronal loss or correlating with terminal NFT load.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1460-9568
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-46
pubmed:meshHeading
pubmed-meshheading:18702695-Alzheimer Disease, pubmed-meshheading:18702695-Animals, pubmed-meshheading:18702695-Animals, Genetically Modified, pubmed-meshheading:18702695-Brain, pubmed-meshheading:18702695-Brain Stem, pubmed-meshheading:18702695-Cell Count, pubmed-meshheading:18702695-Disease Models, Animal, pubmed-meshheading:18702695-Female, pubmed-meshheading:18702695-Gene Expression, pubmed-meshheading:18702695-Hippocampus, pubmed-meshheading:18702695-Humans, pubmed-meshheading:18702695-Longevity, pubmed-meshheading:18702695-Male, pubmed-meshheading:18702695-Neurofibrillary Tangles, pubmed-meshheading:18702695-Neurons, pubmed-meshheading:18702695-Protein Folding, pubmed-meshheading:18702695-Rats, pubmed-meshheading:18702695-Survival Analysis, pubmed-meshheading:18702695-Tauopathies, pubmed-meshheading:18702695-Transgenes, pubmed-meshheading:18702695-tau Proteins
pubmed:year
2008
pubmed:articleTitle
Truncated tau expression levels determine life span of a rat model of tauopathy without causing neuronal loss or correlating with terminal neurofibrillary tangle load.
pubmed:affiliation
Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Dubravska cesta 9, 845 10 Bratislava, Slovak Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't