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(American Journal of Pathology. 2004;164:347-353.)
© 2004 American Society for Investigative Pathology

Animal Model

Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau

Ronald L. Klein*, Wen-Lang Lin{dagger}, Dennis W. Dickson{dagger}, Jada Lewis{ddagger}, Michael Hutton{ddagger}, Karen Duff§, Edwin M. Meyer and Michael A. King||**

From the Department of Pharmacology and Therapeutics,* Louisiana State University Health Sciences Center, Shreveport, Louisiana; the Departments of Pathology{dagger} and Neuroscience,{ddagger} Mayo Clinic, Jacksonville, Florida; the Departments of Pharmacology and Therapeutics and Neuroscience,|| University of Florida College of Medicine and McKnight Brain Institute, Gainesville, Florida; the Malcom Randall Veteran’s Administration Medical Center,** Gainesville, Florida; and the Center for Dementia Research,§ Nathan Kline Institute, Orangeburg, New York

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.






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Copyright © 2004 by the American Society for Investigative Pathology.