Animal models of tauopathies.
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 crosstalk among several pathogenic molecules. Enhancement of tau pathology by amyloid beta (Abeta) deposition provided some of the most compelling evidence for such a cross-talk, and molecular processes linking abnormalities of Abeta and tan 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 alpha-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.
Higuchi
Makoto
M
Brain Imaging Project, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba 263-8555, Japan. mhiguchi@nirs.go.jp
Saido
Takaomi C
TC
Suhara
Tetsuya
T
D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D024801:Tauopathies; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
D051844:alpha-Synuclein; D016875:tau Proteins