title: Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein.
abstract: BACKGROUND
  A possible role of autoimmunity in Alzheimer disease pathogenesis has recently attracted increasing attention. Vaccination with amyloid-beta peptide was reported to cause marked reduction in amyloid deposition, but it also induced encephalitis. Not much is known regarding neurofibrillary tangle-related autoimmune effects.
  
  
  OBJECTIVE
  To use the main component of tangles-microtubule-associated tau protein-to test the feasibility of active induction of a neuroautoimmune disorder in mice.
  
  
  METHODS
  Prospective, randomized controlled animal study.
  
  
  METHODS
  University medical center research laboratory. Subjects Female C57BL/6 mice.
  
  
  METHODS
  Inoculation with recombinant human tau protein emulsified in complete Freund adjuvant and with pertussis toxin.
  
  
  METHODS
  Clinical, immunologic, pathologic, and behavioral evaluations were performed.
  
  
  RESULTS
  Vaccination with tau protein induced histopathologic features of Alzheimer disease and tauopathies, indicated by the presence of neurofibrillary tangle-like structures, axonal damage, and gliosis. Also, mononuclear infiltrates without demyelination in the central nervous system, accompanied by neurologic deficits (such as a limp tail and limb paralysis), were observed. Anti-tau antibodies were detected in the serum of tau-immunized mice.
  
  
  CONCLUSIONS
  These results provide a link between tau autoimmunity and tauopathy-like abnormalities and indicate potential dangers of using tau for immunotherapy. This experimental autoimmune tauopathy-like model is due to a pathogenic immune response against an intraneuronal antigen and is not related to myelin antigens.
authors.affiliation: Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel, AHEPA University Hospital, Thessaloniki, Greece. rosenman@hadassah.org.il
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenmann
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.forename: Moran
authors.initials: M
authors.lastname: Boimel
authors.forename: Olga
authors.initials: O
authors.lastname: Touloumi
authors.forename: Haim
authors.initials: H
authors.lastname: Ovadia
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000503:physiopathology; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016874:Neurofibrillary Tangles / Q000276:immunology* / Q000473:pathology; D010243:Paralysis / Q000276:immunology / Q000503:physiopathology; D014611:Vaccination / Q000009:adverse effects; D014855:Wallerian Degeneration / Q000276:immunology / Q000503:physiopathology; D016875:tau Proteins / Q000009:adverse effects / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016875:tau Proteins