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June 12, 2001; 56 (suppl 4) Articles

Transgenic mouse models of tauopathies: Prospects for animal models of Pick’s disease

Virginia M.-Y. Lee, John Q. Trojanowski
First published June 12, 2001, DOI: https://doi.org/10.1212/WNL.56.suppl_4.S26
Virginia M.-Y. Lee
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John Q. Trojanowski
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Transgenic mouse models of tauopathies: Prospects for animal models of Pick’s disease
Virginia M.-Y. Lee, John Q. Trojanowski
Neurology Jun 2001, 56 (suppl 4) S26-S30; DOI: 10.1212/WNL.56.suppl_4.S26

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Abstract

Because filamentous neuronal tau inclusions are neuropathologic hallmarks of Pick’s disease and a number of other neurodegenerative disorders known as tauopathies, the authors generated lines of transgenic (Tg) mice that overexpress the shortest human tau isoform in the CNS. These Tg mice accumulated argyrophilic and filamentous tau immunoreactive neuronal inclusions with age in cortex and brainstem as well as in spinal cord, where these inclusions were most abundant and associated with gliosis. The ventral roots of affected spinal cord segments showed axonal degeneration, whereas residual axons exhibited reduced microtubules and reduced fast axonal transport. The inclusions were composed of 10 to 20 nm tau immunopositive straight filaments. In addition, the Tg mice developed age-related motor weakness as well as progressive hyperphosphorylation and decreased solubility of brain and spinal cord tau proteins. Thus, these Tg mice recapitulate phenotypic features of human tauopathies. In this article the authors review the phenotype of these Tg mice and discuss how the availability of relevant animal model of tauopathies will facilitate discovery of more effective therapies to treat Pick’s disease and related disorders characterized by filamentous tau pathology in selectively vulnerable regions of the CNS.

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