Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

Kiran Yanamandra, Tirth K. Patel, Hong Jiang, Suzanne Schindler, Jason D. Ulrich, Adam L. Boxer, Bruce L. Miller, Diana R. Kerwin, Gilbert Gallardo, Floy Stewart, Mary Beth Finn, Nigel J. Cairns, Philip B. Verghese, Ilana Fogelman, Tim West, Joel Braunstein, Grace Robinson, Jennifer Keyser, Joseph Roh, Stephanie S. KnapikYan Hu, David M. Holtzman

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. 2017

Original languageEnglish (US)
Article numbereaal2029
JournalScience Translational Medicine
Volume9
Issue number386
DOIs
StatePublished - Apr 19 2017

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy'. Together they form a unique fingerprint.

  • Cite this

    Yanamandra, K., Patel, T. K., Jiang, H., Schindler, S., Ulrich, J. D., Boxer, A. L., Miller, B. L., Kerwin, D. R., Gallardo, G., Stewart, F., Finn, M. B., Cairns, N. J., Verghese, P. B., Fogelman, I., West, T., Braunstein, J., Robinson, G., Keyser, J., Roh, J., ... Holtzman, D. M. (2017). Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy. Science Translational Medicine, 9(386), [eaal2029]. https://doi.org/10.1126/scitranslmed.aal2029