Animal models of tauopathies

Accumulation of intraneuronal amyloid comprised of tau proteins occurs in a group of neurodegenerative disorders, collectively termed tauopathies, and pathological alterations of tau proteins alone are sufficient to cause degeneration of neurons, as compellingly evidenced by discovery of tau gene mutations in kindreds of familial tauopathy known as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Mice modeling tauopathies have been generated by overexpression of human tau with FTDP-17 mutations, in order to gain more profound insights into molecular links between tau abnormalities and neurodegeneration. A subset of these mice were reported to exhibit abundant tau amyloid lesions resembling neurofibrillary changes in human tauopathies, and pronounced neuronal loss notable as progressive brain atrophy. Significantly, formation of mature amyloid fibrils is not tightly associated with neuron death, while deposition of microtubule-unbound phosphorylated tau, which conceivably emerges early in tau fibrillogenesis, appears to critically contribute to disruption of neuronal integrity. In addition to such mechanistic elucidation, mouse models of tauopathies are currently being applied to exploitation of imaging agents for visualization of tau pathologies in living brains. This technology would greatly facilitate diagnostic workup of patients with suspected tauopathies when combined with appropriate imaging modalities.