Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements

• DOI: 10.1523/jneurosci.2361-07.2007
• Publication Date: 2007-08-22T16:23:49Z
• Authors: Ayodeji A. Asuni; Allal Boutajangout; David Quartermain; Einar M. Sigurdsson
• Keywords: Immunogen; Tauopathy; Tau protein; Tangle

Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach clearing pathological protein conformers in these disorders. This type of treatment has not been assessed models that develop neuronal tau aggregates observed frontotemporal dementia and Alzheimer's disease. Here, we present active immunization with phosphorylated epitope, P301L tangle model mice, reduces aggregated the brain slows progression tangle-related behavioral phenotype. Females had more pathology than males but were also receptive to immunotherapy. The antibodies generated animals recognized on sections. Performance assays require extensive motor coordination correlated corresponding areas, antibody levels against immunogen inversely pathology. Interestingly, age-dependent autoantibodies recombinant detected mice. To confirm anti-tau could enter bind tau, FITC-tagged purified from mouse, high titer immunogen, injected into carotid artery These subsequently within colocalized PHF1 MC1 recognize tau. Currently, no is available aggregates. Our findings may lead novel therapy targeting one major hallmarks disease dementia.