Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein

Arch Neurol. 2006 Oct;63(10):1459-67. doi: 10.1001/archneur.63.10.1459.

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.

Design: Prospective, randomized controlled animal study.

Setting: University medical center research laboratory. Subjects Female C57BL/6 mice.

Interventions: Inoculation with recombinant human tau protein emulsified in complete Freund adjuvant and with pertussis toxin.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / immunology*
  • Alzheimer Disease / physiopathology
  • Animals
  • Autoantibodies / immunology
  • Autoimmune Diseases of the Nervous System / immunology*
  • Autoimmune Diseases of the Nervous System / physiopathology
  • Brain / immunology*
  • Brain / pathology
  • Brain / physiopathology
  • Disease Models, Animal
  • Female
  • Gliosis / immunology
  • Gliosis / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Neurofibrillary Tangles / immunology*
  • Neurofibrillary Tangles / pathology
  • Paralysis / immunology
  • Paralysis / physiopathology
  • Vaccination / adverse effects
  • Wallerian Degeneration / immunology
  • Wallerian Degeneration / physiopathology
  • tau Proteins / adverse effects
  • tau Proteins / immunology*

Substances

  • Autoantibodies
  • tau Proteins