title: Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer's Disease and Other Tauopathies.
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.
authors.affiliation: 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.
authors.forename: Sulana K
authors.initials: SK
authors.lastname: Schroeder
authors.affiliation: 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.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Joly-Amado
authors.affiliation: 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.
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Gordon
authors.affiliation: 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. scientist.dave@gmail.com.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000544:Alzheimer Disease / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008822:Mice, Transgenic; D024801:Tauopathies / Q000628:therapy; D016875:tau Proteins / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D016875:tau Proteins
keywords: Active immunization; Dementia; Gallyas; Passive immunization; Tau; Transgenic mice; Vaccination; rTg4510