RT Journal Article
SR Electronic
T1 Tau Immunotherapy Modulates Both Pathological Tau and Upstream Amyloid Pathology in an Alzheimer's Disease Mouse Model
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4857
OP 4868
DO 10.1523/JNEUROSCI.4989-14.2015
VO 35
IS 12
A1 Castillo-Carranza, Diana L.
A1 Guerrero-Muñoz, Marcos J.
A1 Sengupta, Urmi
A1 Hernandez, Caterina
A1 Barrett, Alan D.T.
A1 Dineley, Kelly
A1 Kayed, Rakez
YR 2015
UL http://www.jneurosci.org/content/35/12/4857.abstract
AB 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.