Abeta-specific T-cells reverse cognitive decline and synaptic loss in Alzheimer's mice.
Active and passive Abeta immunotherapy provide behavioral benefits in AD transgenic mice, but they can also induce adverse immune over-activation and neuropathological effects. Here, we show that a restricted Abeta-specific immune re-activation can provide cognitive and pathological benefits to APPsw + PS1 transgenic mice for at least 2 1/2 months. A single infusion of Abeta-specific immune cells from Abeta-vaccinated littermates improved performance in cognitively impaired APP + PS1 mice. Recipients had lower levels of soluble Abeta in the hippocampus, less plaque-associated microglia, and more intense synaptophysin immunoreactivity, compared with untreated controls. However, Abeta-specific infusates enriched for Th1 or depleted of CD4(+) T-cells were not effective, nor were ovalbumin-specific infusates. These benefits occurred without global or brain-specific inflammatory responses. Chronically high levels of Abeta can cause immune tolerance, hypo-responsiveness, or anergy to Abeta, but our findings demonstrate that Abeta-specific immune cells can resume endogenous Abeta-lowering processes and may be an effective Abeta therapeutic.
Ethell
Douglas W
DW
Biomedical Sciences, University of California Riverside, 92521-0121, USA. doug.ethell@ucr.edu
Shippy
Daniel
D
Cao
Chuanhai
C
Cracchiolo
Jennifer R
JR
Runfeldt
Melissa
M
Blake
Brett
B
Arendash
Gary W
GW
D019264:Adoptive Transfer; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D017710:Lymphocyte Transfusion; D051379:Mice; D008822:Mice, Transgenic; D013569:Synapses / Q000473:pathology*; D016708:Synaptophysin / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D016229:Amyloid beta-Peptides; D016708:Synaptophysin