| First Author | Seino Y | Year | 2010 |
| Journal | J Neurosci Res | Volume | 88 |
| Issue | 16 | Pages | 3547-54 |
| PubMed ID | 20936700 | Mgi Jnum | J:274035 |
| Mgi Id | MGI:6295590 | Doi | 10.1002/jnr.22516 |
| Citation | Seino Y, et al. (2010) Amyloid beta accelerates phosphorylation of tau and neurofibrillary tangle formation in an amyloid precursor protein and tau double-transgenic mouse model. J Neurosci Res 88(16):3547-54 |
| abstractText | In Alzheimer's disease, Abeta deposits are considered the initial cardinal events that induce tauopathy secondarily. However, the relationship between Abeta amyloidosis and tauopathy has not been determined in detail. We produced double transgenic mice, 2xTgTau(+/-) APP(+/-) , by mating Tg2576 mice that exhibit Abeta amyloidosis and TgTauP301L mice that show tauopathy, and statistically analyzed the effect of Abeta accumulation on tauopathy. There was no significant difference in theprogression of Abeta accumulation among 2xTgTau(+/-) APP(+/-) and 1xTgTau(-/-) APP(+/-) , and tau accumulation among 2xTgTau(+/-) APP(+/-) and 1xTg Tau(+/-) APP(-/-) . The appearance rates of phosphorylated tau developing in neurons and processes were significantly accelerated in 2xTgTau(+/-) APP(+/-) mice compared with those in 1xTgTau(+/-) APP(-/-) mice at 23 months of age. Accumulation of phosphorylated and confomationally altered tau and GSK3beta in neuronal processes was accelerated in the white matter in 2xTgTau(+/-) APP(+/-) . The level of phosphorylated tau in the sarkosyl-insoluble fraction was increased in 2xTgTau(+/-) APP(+/-) brains compared with that in 1xTgTau(+/-) APP(-/-) brains. Thus, Abeta amyloid partially enhances tauopathy through accumulation of insoluble, phosphorylated, and conformationally changed tau in neuronal cytoplasm and processes in the late stage. |
