Animal models of tauopathies
Article first published online: 27 SEP 2006
Volume 26, Issue 5, pages 491–497, October 2006
How to Cite
Higuchi, M., Saido, T. C. and Suhara, T. (2006), Animal models of tauopathies. Neuropathology, 26: 491–497. doi: 10.1111/j.1440-1789.2006.00685.x
- Issue published online: 27 SEP 2006
- Article first published online: 27 SEP 2006
- Received 19 October 2005; accepted 24 October 2005.
- Alzheimer’s disease;
- amyloid imaging;
- frontotemporal lobar degeneration;
- neurofibrillary tangle
Intracellular fibrillar amyloid lesions comprised of tau proteins are pathological hallmarks in diverse neurodegenerative disorders. As models of these tauopathies, transgenic mice overexpressing tau with or without mutations discovered in familial tauopathies were generated. Findings in these tau transgenic mice support the notion that impairments of tau proteins are causally related to tauopathies, while studies on crossbred mice have indicated initiation and promotion of tau-positive neuropathologies by cross-talk among several pathogenic molecules. Enhancement of tau pathology by amyloid β (Aβ) deposition provided some of the most compelling evidence for such a cross-talk, and molecular processes linking abnormalities of Aβ and tau have been suggested to involve activation of calcium-dependent protease, calpain, based on analyses of amyloid precursor protein transgenic mice crossbred with other genetically engineered mice with altered calpain activity. It also should be noted that mice transgenic for both tau and α-synuclein exhibit facilitated polymerization of these molecules into pathological filaments. Roles of fibrillar tau deposits in nervous system injuries can be mechanistically pursued by longitudinal monitoring of brain amyloidosis and neuroglial degeneration in the time course of antiamyloid intervention. The possibility of in vivo detection of tau-positive amyloid lesions has been demonstrated by intravenous administration of potential tracers into tau transgenic mice and subsequent brain imaging. Moreover, visualization of glial responses in living brains may allow sensitive detection of degenerative changes in the central nervous system.