Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies

• Published in: PloS one Vol. 10; no. 8; p. e0135774
• Main Authors: d'Abramo, Cristina, Acker, Christopher M, Jimenez, Heidy, Davies, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-08-2015; Public Library of Science (PLoS)
• Subjects: Alzheimer's disease; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Phospho-Specific - administration & dosage; Antibodies, Phospho-Specific - therapeutic use; Antigenic determinants; Brain; Brain research; Disease Models, Animal; Epitopes; Female; Hindbrain; Homogenization; Humans; Immunization; Immunization (passive); Immunization, Passive - methods; Immunoglobulins; Immunotherapy; In vivo methods and tests; Injections, Intraperitoneal; Medical research; Mice; Mice, Transgenic; Monoclonal antibodies; Mutation; Pathology; Phosphorylation; Phosphorylation - drug effects; Proteins; Rhombencephalon - metabolism; Rodents; Tau protein; tau Proteins - genetics; tau Proteins - immunology; tau Proteins - metabolism; Tauopathies - genetics; Tauopathies - immunology; Tauopathies - therapy; Transgenic animals; Transgenic mice; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0135774

Recent work from our lab and few others have strongly suggested that immunotherapy could be an effective means of preventing the development of tau accumulation in JNPL3 transgenic mice, carrying the human P301L mutation. The aim of this study was to test the efficacy of a variety of specific tau monoclonal antibodies in JNPL3. Starting at 3 months of age, mice were treated for 4 months with weekly intraperitoneal injections of saline or purified tau monoclonal antibodies (10 mg/Kg) different in specificity for pathological tau: CP13 (pSer202), RZ3 (pThr231) and PG5 (pSer409). As expected, not all the antibodies tested showed efficacy at preventing the development of tau pathology at the described dose, with some of them even worsening the pathological scenario. Only by targeting the pSer202 epitope with CP13 was a conspicuous reduction of insoluble or soluble tau in cortex and hindbrain obtained. Here we report about the importance of screening in vivo multiple tau antibodies in order to select the antibodies to direct into future clinical studies.