Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 22, Pages 5446-5454Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4637-04.2005
Keywords
cell cycle; neurofibrillary tangle; cell death; transgenic; nonmutant tau; neurodegeneration
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Funding
- NIA NIH HHS [R37 AG022102, R01 AG022102, AG022102] Funding Source: Medline
- PHS HHS [38623] Funding Source: Medline
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Mutations in the microtubule-associated protein tau gene have been linked to neurofibrillary tangle (NFT) formation in several neuro-degenerative diseases known as tauopathies; however, no tau mutations occur in Alzheimer's disease, although this disease is also characterized by NFT formation and cell death. Importantly, the mechanism of tau-mediated neuronal death remains elusive. Aged mice expressing nonmutant human tau in the absence of mouse tau (htau mice) developed NFTs and extensive cell death. The mechanism of neuron death was investigated in htau mice, and surprisingly, the presence of tau filaments did not correlate directly with death within individual cells, suggesting that cell death can occur independently of NFT formation. Our observations show that the mechanism of neurodegeneration involved reexpression of cell-cycle proteins and DNA synthesis, indicating that nonmutant tau pathology and neurodegeneration may be linked via abnormal, incomplete cell-cycle reentry.
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