The role of tau gene mutations in neurodegenerative disease

Mutations in the tau gene lead to the abnormal aggregation of tau protein and the onset/progression of frontotemporal dementia. This finding demonstrates a role for tau production dysregulation in neurodegenerative disease. The six isoforms of tau found in Alzheimer’s disease contain either three (3R) or four (4R) microtubule-binding domains. Mutations in exon 10 result in alternative splicing of the tau gene and an increase in the proportion of 4R tau isoforms. This change is sufficient to produce nerve cell and glial cell dysfunction, leading to tau filament formation and degeneration. Tau mutations are thought to be instrumental in many neurodegenerative disorders, including Alzheimer’s disease.

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References

PNAS 1998;95:7737–7741.

Brain Pathol 1999;9:681–693.

J Neurochem 2000;74:1749–1757.

Med Clin North Am 2002;86:615–627.