Vaccination with Sarkosyl Insoluble PHF-Tau Decrease Neurofibrillary Tangles Formation in Aged Tau Transgenic Mouse Model: A Pilot Study

Issue title: Propagation of Tau Pathology

Guest editors: Miguel Medina and Jesús Avila

Article type: Research Article

Authors: Ando, Kunie^{a; b; c; 1} | Kabova, Anna^{a; 1} | Stygelbout, Virginie^a | Leroy, Karelle^a | Heraud, Céline^a | Frédérick, Christelle^a | Suain, Valérie^a | Yilmaz, Zehra^a | Authelet, Michèle^a | Dedecker, Robert^a | Potier, Marie-Claude^c | Duyckaerts, Charles^{b; c} | Brion, Jean-Pierre^{a; *}

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

Correspondence: [*] Correspondence to: Dr. Jean-Pierre Brion, Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, School of Medicine. 808, route de Lennik, Bldg GE, 1070 – Brussels, Belgium. Tel.: +32 2 5556505; Fax: +32 2 5556285; E-mail: [email protected].

Note: [1] These authors equally contributed to this work.

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.

Keywords: Alzheimer's disease, neurofibrillary tangles, paired helical filaments-tau, tau vaccination

DOI: 10.3233/JAD-132237

Journal: Journal of Alzheimer's Disease, vol. 40, no. s1, pp. S135-S145, 2014