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Sci Transl Med. 2017 Apr 19;9(386). pii: eaal2029. doi: 10.1126/scitranslmed.aal2029.

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

Author information

1
Hope Center for Neurological Disorders and Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University, St. Louis, MO 63110,USA.
2
AbbVie Inc. Foundational Neuroscience Center, Cambridge, MA 02139, USA.
3
Clinical Trials Program, Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Texas Alzheimer's and Memory Disorders, Texas Health Presbyterian Hospital Dallas, Dallas, TX 75231, USA.
5
C2N Diagnostics, Center for Emerging Technologies, 4041 Forest Park Avenue, St. Louis, MO 63108, USA.
6
Hope Center for Neurological Disorders and Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University, St. Louis, MO 63110,USA. holtzman@neuro.wustl.edu.

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.

PMID:
28424326
PMCID:
PMC5727571
DOI:
10.1126/scitranslmed.aal2029
[Indexed for MEDLINE]
Free PMC Article

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