Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau

Ronald L. Klein, Wen Lang Lin, Dennis W. Dickson, Jada Lewis, Michael Hutton, Karen Duff, Edwin M. Meyer, Michael A. King

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Neurofibrillary pathology was produced in the brains of adult rats after localized gene transfer of human tau carrying the P301L mutation, which is associated with frontotemporal dementia with parkinsonism. Within 1 month of in situ transfection of the basal forebrain region of normal rats, tau-immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions had features of neurofibrillary tangles and tau immunoreactivity at light and electron microscopic levels. In addition to neurofibrillary tangles, other tau pathology, including pretangles and neuropil threads, was abundant and widespread. Tau gene transfer to the hippocampal region of amyloid-depositing transgenic mice produced pretangles and threads, as well as intensely tau-immunoreactive neurites in amyloid plaques. The ability to produce neurofibrillary pathology in adult rodents makes this a useful method to study tau-related neurodegeneration.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalAmerican Journal of Pathology
Volume164
Issue number1
DOIs
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Klein, R. L., Lin, W. L., Dickson, D. W., Lewis, J., Hutton, M., Duff, K., Meyer, E. M., & King, M. A. (2004). Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau. American Journal of Pathology, 164(1), 347-353. https://doi.org/10.1016/S0002-9440(10)63124-0