2006
DOI: 10.2353/ajpath.2006.050840
|View full text |Cite
|
Sign up to set email alerts
|

Region-specific Dissociation of Neuronal Loss and Neurofibrillary Pathology in a Mouse Model of Tauopathy

Abstract: Neurofibrillary tangles form in a specific spatial and temporal pattern in Alzheimer's disease. Although tangle formation correlates with dementia and neuronal loss, it remains unknown whether neurofibrillary pathology causes cell death. Recently, a mouse model of tauopathy was developed that reversibly expresses human tau with the dementia-associated P301L mutation. This model (rTg4510) exhibits progressive behavioral deficits that are ameliorated with transgene suppression. Using quantitative analysis of PHF… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

28
337
2
1

Year Published

2008
2008
2015
2015

Publication Types

Select...
6
2

Relationship

3
5

Authors

Journals

citations
Cited by 361 publications
(368 citation statements)
references
References 45 publications
28
337
2
1
Order By: Relevance
“…Phosphorylated tau stabilizes the internal structure of healthy neurons, but in AD, tau proteins are hyperphosphorylated and tangle together. Again, recent evidence points to soluble tau rather than NFT as a cause of neuronal loss in AD [18][19][20]. When researchers turned off the mutant tau gene in a mouse model of AD, neurodegeneration was halted and cognitive performance improved even though NFT continued to accumulate [19].…”
Section: Alzheimer's Diseasementioning
confidence: 99%
“…Phosphorylated tau stabilizes the internal structure of healthy neurons, but in AD, tau proteins are hyperphosphorylated and tangle together. Again, recent evidence points to soluble tau rather than NFT as a cause of neuronal loss in AD [18][19][20]. When researchers turned off the mutant tau gene in a mouse model of AD, neurodegeneration was halted and cognitive performance improved even though NFT continued to accumulate [19].…”
Section: Alzheimer's Diseasementioning
confidence: 99%
“…In histologic studies, NFTs are associated with immunohistochemical evidence of caspase activation and caspase-cleavage products, leading to the hypothesis that NFTs cause apoptotic death (Gamblin et al, 2003;Rissman et al, 2004). However, some data from cell culture experiments, mouse models, and disease caused by tau mutations that causes cell death but not tangle formation indicate that protein inclusions may be unnecessary for neuronal death or even protect cells from toxic soluble moieties (Saudou et al, 1998;Reed et al, 2001;Bodner et al, 2006;Spires et al, 2006).…”
Section: Introductionmentioning
confidence: 99%
“…Pearson's correlations and Fisher's r to z ( p values) comparing caspase eight levels and neuron number (Spires et al, 2006) were calculated using StatView (SAS Institute, Cary, NC). To compare transgenic to control levels of caspase eight normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) levels, Mann-Whitney U tests were used (caspase mRNA data were not normally distributed).…”
Section: Surgery and Imagingmentioning
confidence: 99%
See 1 more Smart Citation
“…Discussion NFT-bearing neurons are characterized by abnormal accumulation of fibrillar tau aggregates in the cell soma and proximal dendrites compared with the predominantly axonal localization of tau in healthy neurons (24). To isolate the consequences of tau aggregation and mislocalization to soma and dendrites (6), we focused on the primary visual cortex, a brain area in which the major driving input source, the lateral geniculate nucleus, is structurally intact (10,25) (Fig. S7).…”
Section: Significancementioning
confidence: 99%