Pharmacology, Toxicology and Environmental Health Commons^™

Vectored Intracerebral Immunization With The Anti-Tau Monoclonal Antibody Phf1 Markedly Reduces Tau Pathology In Mutant Tau Transgenic Mice, Wencheng Liu, Lingzhi Zhao, Brittany Blackman, Mayur Parmar, Man Ying Wong, Thomas Woo, Fangmin Yu, Maria J. Chiuchiolo, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal, Steven M. Paul

HPD Articles

UNLABELLED: Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic …