title: Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA. klein@lsuhsc.edu
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Klein
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Lin
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Jada
authors.initials: J
authors.lastname: Lewis
authors.forename: Michael
authors.initials: M
authors.lastname: Hutton
authors.forename: Karen
authors.initials: K
authors.lastname: Duff
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D024801:Tauopathies / Q000235:genetics / Q000473:pathology*; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D016875:tau Proteins