This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on ISI (3)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Movement Disorders  • Neurology, Other  • Public Health  • Immunization  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic

Hanna Rosenmann, PhD; Nikolaos Grigoriadis, MD, PhD; Dimitrios Karussis, MD, PhD; Moran Boimel, BSc; Olga Touloumi, BSc; Haim Ovadia, PhD; Oded Abramsky, MD, PhD

Arch Neurol. 2006;63:1459-1467.

Background  A possible role of autoimmunity in Alzheimer disease pathogenesis has recently attracted increasing attention. Vaccination with amyloid- 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.

Author Affiliations: Departments of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel (Drs Rosenmann, Karussis, Ovadia, and Abramsky and Ms Boimel), AHEPA University Hospital, Thessaloniki, Greece (Dr Grigoriadis and Ms Touloumi).