| First Author | Terwel D | Year | 2008 |
| Journal | Am J Pathol | Volume | 172 |
| Issue | 3 | Pages | 786-98 |
| PubMed ID | 18258852 | Mgi Jnum | J:132009 |
| Mgi Id | MGI:3774952 | Doi | 10.2353/ajpath.2008.070904 |
| Citation | Terwel D, et al. (2008) Amyloid Activates GSK-3{beta} to Aggravate Neuronal Tauopathy in Bigenic Mice. Am J Pathol 172(3):786-98 |
| abstractText | The hypothesis that amyloid pathology precedes and induces the tau pathology of Alzheimer's disease is experimentally supported here through the identification of GSK-3 isozymes as a major link in the signaling pathway from amyloid to tau pathology. This study compares two novel bigenic mouse models: APP-V717I x Tau-P301L mice with combined amyloid and tau pathology and GSK-3beta x Tau-P301L mice with tauopathy only. Extensive and remarkable parallels were observed between these strains including 1) aggravation of tauopathy with highly fibrillar tangles in the hippocampus and cortex; 2) prolonged survival correlated to alleviated brainstem tauopathy; 3) development of severe cognitive and behavioral defects in young adults before the onset of amyloid deposition or tauopathy; and 4) presence of pathological phospho-epitopes of tau, including the characteristic GSK-3beta motif at S396/S404. Both GSK-3 isozymes were activated in the brain of parental APP-V717I amyloid mice, even at a young age when cognitive and behavioral defects are evident but before amyloid deposition. The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons. |
