Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an alzheimer’s disease mouse model

Diana L. Castillo-Carranza, Marcos J. Guerrero-Muñoz, Urmi Sengupta, Caterina Hernandez, Alan D.T. Barrett, Kelly Dineley, Rakez Kayed

Research output: Contribution to journalArticle

79 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4857-4868
Number of pages12
JournalJournal of Neuroscience
Volume35
Issue number12
DOIs
StatePublished - 2015

Keywords

  • Alzheimer’s disease
  • Aβ*56
  • Immunotherapy
  • Tau oligomers
  • Tg2576

ASJC Scopus subject areas

  • Neuroscience(all)

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    Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Hernandez, C., Barrett, A. D. T., Dineley, K., & Kayed, R. (2015). Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an alzheimer’s disease mouse model. Journal of Neuroscience, 35(12), 4857-4868. https://doi.org/10.1523/JNEUROSCI.4989-14.2015