title: Vaccination with Sarkosyl insoluble PHF-tau decrease neurofibrillary tangles formation in aged tau transgenic mouse model: a pilot study.
abstract: Active immunization using tau phospho-peptides in tauopathy mouse models has been observed to reduce tau pathology, especially when given prior to the onset of pathology. Since tau aggregates in these models and in human tauopathies are composed of full-length tau with many post-translational modifications, and are composed of several tau isoforms in many of them, pathological tau proteins bearing all these post-translational modifications might prove to be optimal tau conformers to use as immunogens, especially in models with advanced tau pathology. To this aim, we immunized aged wild-type and mutant tau mice with preparations containing human paired helical filaments (PHF) emulsified in Alum-adjuvant. This immunization protocol with fibrillar PHF-tau was well tolerated and did not induce an inflammatory reaction in the brain or adverse effect in these aged mice. Mice immunized with four repeated injections developed anti-PHF-tau antibodies with rising titers that labeled human neurofibrillary tangles in situ. Immunized mutant tau mice had a lower density of hippocampal Gallyas-positive neurons. Brain levels of Sarkosyl-insoluble tau were also reduced in immunized mice. These results indicate that an immunization protocol using fibrillar PHF-tau proteins is an efficient and tolerated approach to reduce tau pathology in an aged tauopathy animal model.
authors.affiliation: Laboratory 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.
authors.forename: Kunie
authors.initials: K
authors.lastname: Ando
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Kabova
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Stygelbout
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Karelle
authors.initials: K
authors.lastname: Leroy
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Heraud
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christelle
authors.initials: C
authors.lastname: Frédérick
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Suain
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Yilmaz
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Michèle
authors.initials: M
authors.lastname: Authelet
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Dedecker
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Potier
authors.affiliation: 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.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Brion
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D012521:Sarcosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014611:Vaccination; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins; C025231:sarkosyl; D012521:Sarcosine
keywords: Alzheimer's disease; neurofibrillary tangles; paired helical filaments-tau; tau vaccination