. Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci. 2010 Dec 8;30(49):16559-66. PubMed.

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  1. Boutajangout et al. demonstrate that targeting phosphorylated tau by active immunization prevents cognitive decline in their new htau/PS1 mouse model. This is the third study demonstrating the efficacy of active vaccination using phosphorylated tau fragments in different animal models and confirms their (Asuni et al., 2007) and other previous findings (Boimel et al., 2010). The authors did an outstanding job in sensorimotor and memory testing of all groups; still, the biochemical analysis of the vaccinated and unvaccinated animals is incomplete.

    The authors vaccinated the new model with the same immunogen use in the their earlier study (Asuni et al. 2007), the tau fragment (379-408) phosphorylated at Ser396 and Ser404. What is surprising and worrying is the antibody response (Figure 1A). Although the initial response at T1(one week) showed high antibody response toward the phosphorylated sequence (tau 379-408), after several boosts, the antibody response was stronger toward the unphosphorylated sequence (tau 379-408) than the phosphorylated sequence at the end of the study (Tf). That may lead to the depletion of functional tau and may interfere with its functions and cause other complications.

    References:

    . Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci. 2007 Aug 22;27(34):9115-29. PubMed.

    . Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp Neurol. 2010 Aug;224(2):472-85. PubMed.

    . Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci. 2007 Aug 22;27(34):9115-29. PubMed.

  2. We thank Rakez for his comment.

    Antibody response towards non-phosphorylated regions of the immunogen can be expected considering its length and immunogenicity. This should not cause major concerns, as we address in the fourth paragraph of the Discussion (pp. 16564-5). However, we are certainly looking more closely into this interesting issue.