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Arch Neurol. 2006 Oct;63(10):1459-67.

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

Author information

  • 1Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel, AHEPA University Hospital, Thessaloniki, Greece. rosenman@hadassah.org.il

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.

PMID:
17030663
[PubMed - indexed for MEDLINE]
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