| First Author | Rajamohamedsait H | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 17034 |
| PubMed ID | 29213096 | Mgi Jnum | J:287381 |
| Mgi Id | MGI:6407482 | Doi | 10.1038/s41598-017-17313-1 |
| Citation | Rajamohamedsait H, et al. (2017) Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-beta Pathologies in 3xTg Mice. Sci Rep 7(1):17034 |
| abstractText | Amyloid-beta (Abeta) and tau pathologies are intertwined in Alzheimer's disease, and various immunotherapies targeting these hallmarks are in clinical trials. To determine if tau pathology influences Abeta burden and to assess prophylactic benefits, 3xTg and wild-type mice received tau immunization from 2-6 months of age. The mice developed a high IgG titer that was maintained at 22 months of age. Pronounced tau and Abeta pathologies were primarily detected in the subiculum/CA1 region, which was therefore the focus of analysis. The therapy reduced histopathological tau aggregates by 70-74% overall (68% in males and 78-86% in females), compared to 3xTg controls. Likewise, western blot analysis revealed a 41% clearance of soluble tau (38-76% in males and 48% in females) and 42-47% clearance of insoluble tau (47-58% in males and 49% in females) in the immunized mice. Furthermore, Abeta burden was reduced by 84% overall (61% in males and 97% in females). These benefits were associated with reductions in microgliosis and microhemorrhages. In summary, prophylactic tau immunization not only prevents tau pathology but also Abeta deposition and related pathologies in a sustained manner, indicating that tau pathology can promote Abeta deposition, and that a short immunization regimen can have a long-lasting beneficial effect. |
