| First Author | Walls KC | Year | 2014 |
| Journal | Neurosci Lett | Volume | 575 |
| Pages | 96-100 | PubMed ID | 24887583 |
| Mgi Jnum | J:214748 | Mgi Id | MGI:5603961 |
| Doi | 10.1016/j.neulet.2014.05.047 | Citation | Walls KC, et al. (2014) p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice. Neurosci Lett 575:96-100 |
| abstractText | Alzheimer's disease (AD) is a proteinopathy characterized by the accumulation of beta-amyloid (Abeta) and tau. To date, clinical trials indicate that Abeta immunotherapy does not improve cognition. Consequently, it is critical to modulate other aspects of AD pathology. As such, tau represents an excellent target, as its accumulation better correlates with cognitive impairment. To determine the effectiveness of targeting pathological tau, with Abeta pathology present, we administered a single injection of AT8, or control antibody, into the hippocampus of aged 3xTg-AD mice. Extensive data indicates that phosphorylated Ser(202) and Thr(205) sites of tau (corresponding to the AT8 epitope) represent a pathologically relevant target for AD. We report that immunization with AT8 reduced somatodendritic tau load, p-tau immunoreactivity, and silver stained positive neurons, without affecting Abeta pathology. We also discovered that tau pathology soon reemerges post-injection, possibly due to persistent Abeta pathology. These studies provide evidence that targeting p-tau may represent an effective treatment strategy: potentially in conjunction with Abeta immunotherapy. |
