| First Author | El Khoury NB | Year | 2016 |
| Journal | Neurobiol Dis | Volume | 88 |
| Pages | 55-65 | PubMed ID | 26777665 |
| Mgi Jnum | J:230873 | Mgi Id | MGI:5766404 |
| Doi | 10.1016/j.nbd.2016.01.005 | Citation | El Khoury NB, et al. (2016) Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice. Neurobiol Dis 88:55-65 |
| abstractText | Accumulating evidence from epidemiological studies suggest that type 2 diabetes is linked to an increased risk of Alzheimer's disease (AD). However, the consequences of type 2 diabetes on AD pathologies, such as tau hyperphosphorylation, are not well understood. Here, we evaluated the impact of type 2 diabetes on tau phosphorylation in db/db diabetic mice aged 4 and 26weeks. We found increased tau phosphorylation at the CP13 epitope correlating with a deregulation of c-Jun. N-terminal kinase (JNK) and Protein Phosphatase 2A (PP2A) in 4-week-old db/db mice. 26-week-old db/db mice displayed tau hyperphosphorylation at multiple epitopes (CP13, AT8, PHF-1), but no obvious change in kinases or phosphatases, no cleavage of tau, and no deregulation of central insulin signaling pathways. In contrast to younger animals, 26-week-old db/db mice were hypothermic and restoration of normothermia rescued phosphorylation at most epitopes. Our results suggest that, at early stages of type 2 diabetes, changes in tau phosphorylation may be due to deregulation of JNK and PP2A, while at later stages hyperphosphorylation is mostly a consequence of hypothermia. These results provide a novel link between diabetes and tau pathology, and underlie the importance of recording body temperature to better understand the relationship between diabetes and AD. |
