| First Author | Yetman MJ | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 4 | Pages | e0153724 |
| PubMed ID | 27070146 | Mgi Jnum | J:253550 |
| Mgi Id | MGI:6092810 | Doi | 10.1371/journal.pone.0153724 |
| Citation | Yetman MJ, et al. (2016) Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction. PLoS One 11(4):e0153724 |
| abstractText | Alzheimer's disease (AD) researchers have struggled for decades to draw a causal link between extracellular Abeta aggregation and intraneuronal accumulation of microtubule-associated protein tau. The amyloid cascade hypothesis posits that Abeta deposition promotes tau hyperphosphorylation, tangle formation, cell loss, vascular damage, and dementia. While the genetics of familial AD and the pathological staging of sporadic disease support this sequence of events, attempts to examine the molecular mechanism in transgenic animal models have largely relied on models of other inherited tauopathies as the basis for testing the interaction with Abeta. In an effort to more accurately model the relationship between Abeta and wild-type tau in AD, we intercrossed mice that overproduce human Abeta with a tau substitution model in which all 6 isoforms of the human protein are expressed in animals lacking murine tau. We selected an amyloid model in which pathology was biased towards the entorhinal region so that we could further examine whether the anticipated changes in tau phosphorylation occurred at the site of Abeta deposition or in synaptically connected regions. We found that Abeta and tau had independent effects on locomotion, learning, and memory, but found no behavioral evidence for an interaction between the two transgenes. Moreover, we saw no indication of amyloid-induced changes in the phosphorylation or aggregation of human tau either within the entorhinal area or elsewhere. These findings suggest that robust amyloid pathology within the medial temporal lobe has little effect on the metabolism of wild type human tau in this model. |
