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Vaccination with Sarkosyl insoluble PHF-tau decrease neurofibrillary tangles formation in aged tau transgenic mouse

Kunie Ando1, Anna Kabova2, Virginie Stygelbout2

  • 1Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium Laboratoire de Neuropathologie Escourolle, Hôpital de la Pitiére-Salpêtrière, AP-HP, Paris, France Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France.

Journal of Alzheimer'S Disease : JAD
|March 12, 2014
PubMed
Summary

Active immunization with fibrillar tau proteins effectively reduced tau pathology in aged mice. This approach was well-tolerated and shows promise for treating tauopathies.

Keywords:
Alzheimer's diseaseneurofibrillary tanglespaired helical filaments-tautau vaccination

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Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Tau pathology, characterized by aggregated tau proteins, is a hallmark of tauopathies.
  • Active immunization with tau phospho-peptides reduced tau pathology in models before disease onset.
  • Pathological tau, including full-length tau with post-translational modifications, may be optimal immunogens for advanced pathology.

Purpose of the Study:

  • To evaluate the efficacy and tolerability of immunizing aged mice with fibrillar human paired helical filaments (PHF)-tau.
  • To assess the impact of PHF-tau immunization on existing tau pathology in a tauopathy model.

Main Methods:

  • Aged wild-type and mutant tau mice were immunized with human PHF-tau emulsified in Alum-adjuvant.
  • Four repeated injections were administered.
  • Immunization outcomes were assessed by antibody titers, brain histology (Gallyas staining), and Sarkosyl-insoluble tau levels.

Main Results:

  • The PHF-tau immunization protocol was well-tolerated, with no observed brain inflammation or adverse effects.
  • Immunized mice developed anti-PHF-tau antibodies that labeled neurofibrillary tangles.
  • Mutant tau mice showed reduced Gallyas-positive neurons and lower brain levels of Sarkosyl-insoluble tau.

Conclusions:

  • Immunization with fibrillar PHF-tau proteins is an efficient and safe approach to reduce tau pathology.
  • This strategy is effective even in aged tauopathy models with established pathology.
  • PHF-tau immunization represents a promising therapeutic strategy for tauopathies.