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

T Ishihara, M Hong, B Zhang, Y Nakagawa, MK Lee… - Neuron, 1999 - cell.com
T Ishihara, M Hong, B Zhang, Y Nakagawa, MK Lee, JQ Trojanowski, VMY Lee
Neuron, 1999cell.com
Filamentous tau aggregates are hallmarks of tauopathies, eg, 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 …
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).
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