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Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer’s Disease and Other Tauopathies

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Abstract

Immunotherapy directed against tau is a promising treatment strategy for Alzheimer’s Disease (AD) and tauopathies. We review initial studies on tau-directed immunotherapy, and present data from our laboratory testing antibodies using the rTg4510 mouse model, which deposits tau in forebrain neurons. Numerous antibodies have been tested for their efficacy in treating both pathology and cognitive function, in different mouse models, by different routes of administration, and at different ages or durations. We report, here, that the conformation-specific antibody MC-1 produces some degree of improvement to both cognition and pathology in rTg4510. Pathological improvements as measured by Gallyas staining for fully formed tangles and phosphorylated tau appeared 4 days after intracranial injection into the hippocampus. We also examined markers for microglial activation, which did not appear impacted from treatment. Behavioral effects were noted after continuous infusion of antibodies into the lateral ventricle for approximately 2 weeks. We examined basic motor skills, which were not impacted by treatment, but did note cognitive improvements with both novel object and radial arm water maze testing. Our results support earlier reports in the initial review presented here, and collectively show promise for this strategy of treatment. The general absence of extracellular tau deposits may avoid the opsonization and phagocytosis mechanisms activated by antibodies against amyloid, and make anti tau approaches a safer method of immunotherapy for Alzheimer’s disease.

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Acknowledgments

The authors thank Dr. Peter Davies for the generous gifts of monoclonal antibodies MC-1, PHF1 and DA9, for the treatments reported above. We also thank the vivarium staff at the USF Health Byrd Alzheimer’s Disease Institute for their help in maintaining the health and care of our mouse colony, including maintaining ethical standards and compliance as described in the “Guide for the Care and Use of Laboratory Animals” in an AAALAC-accredited facility. All procedures using mice were approved by the Institutional Animal Care and Use Committee of the University of South Florida. All applicable international, and/or institutional guidelines for the care and use of animals were followed. This work was supported by NS076308 and by the USF Health Byrd Alzheimer’s Institute.

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  1. Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Byrd Alzheimer’s Institute, 4001 E. Fletcher Avenue, Tampa, FL, 33613, USA

    Sulana K. Schroeder, Aurelie Joly-Amado, Marcia N. Gordon & Dave Morgan

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  1. Sulana K. Schroeder
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  2. Aurelie Joly-Amado
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Correspondence to Dave Morgan.

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Schroeder, S.K., Joly-Amado, A., Gordon, M.N. et al. Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer’s Disease and Other Tauopathies. J Neuroimmune Pharmacol 11, 9–25 (2016). https://doi.org/10.1007/s11481-015-9637-6

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