title: Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model.
abstract: In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ). However, the relationship between these two proteins and memory loss is unclear. In this study, we evaluated the specific removal of pathological tau oligomers in aged Tg2576 mice by passive immunotherapy using tau oligomer-specific monoclonal antibody. Removal of tau oligomers reversed memory deficits and accelerated plaque deposition in the brain. Surprisingly, Aβ*56 levels decreased, suggesting a link between tau and Aβ oligomers in the promotion of cognitive decline. The results suggest that tau oligomerization is not only a consequence of Aβ pathology but also a critical mediator of the toxic effects observed afterward in AD. Overall, these findings support the potential of tau oligomers as a therapeutic target for AD.
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and.
authors: Diana L
authors: DL
authors: Castillo-Carranza
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and.
authors: Marcos J
authors: MJ
authors: Guerrero-Muñoz
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and.
authors: Urmi
authors: U
authors: Sengupta
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and.
authors: Caterina
authors: C
authors: Hernandez
authors: Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555.
authors: Alan D T
authors: AD
authors: Barrett
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and.
authors: Kelly
authors: K
authors: Dineley
authors: Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, Neuroscience and Cell Biology, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555 rakayed@utmb.edu.
authors: Rakez
authors: R
authors: Kayed
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D058225:Plaque, Amyloid / Q000378:metabolism; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D016875:tau Proteins
keywords: Alzheimer's disease; Aβ*56; Tau oligomers; Tg2576; immunotherapy