Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform

Takeshi Ishihara, Ming Hong, Bin Zhang, Yasushi Nakagawa, Michael K. Lee, John Q. Trojanowski, Virginia M.Y. Lee

Research output: Contribution to journalArticle

474 Scopus citations

Abstract

Filamentous tau aggregates are hallmarks of tauopathies, e.g., frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC). Since FTDP-17 tau gene mutations alter levels/functions of tau, we overexpressed the smallest human tau isoform in the CNS of transgenic (Tg) mice to model tauopathies. These mice acquired age-dependent CNS pathology similar to FTDP-17 and ALS/PDC, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These Tg mice recapitulate key features of tauopathies and provide models for elucidating mechanisms underlying diverse tauopathies, including Alzheimer's disease (AD).

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalNeuron
Volume24
Issue number3
DOIs
StatePublished - Nov 1999

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