Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau.
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.
Klein
Ronald L
RL
Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA. klein@lsuhsc.edu
Lin
Wen-Lang
WL
Dickson
Dennis W
DW
Lewis
Jada
J
Hutton
Michael
M
Duff
Karen
K
Meyer
Edwin M
EM
King
Michael A
MA
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
D016875:tau Proteins