Epitopes described in "Abeta-specific T-cells reverse cognitive decline and synaptic loss in Alzheimer's mice."

Article Authors:Douglas W Ethell; Daniel Shippy; Chuanhai Cao; Jennifer R Cracchiolo; Melissa Runfeldt; Brett Blake; Gary W Arendash
Article Title:Abeta-specific T-cells reverse cognitive decline and synaptic loss in Alzheimer's mice.
Reference Detail
Reference ID:1021119
Abstract: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.
Affiliations:Biomedical Sciences, University of California Riverside, 92521-0121, USA. doug.ethell@ucr.edu
Reference Type:Literature
PubMed ID:16733088
Journal:Neurobiol Dis
Journal Volume:23
Article Pages:351-61
Journal ISSN:0969-9961
Article Chemical List:Amyloid beta-Peptides;Synaptophysin
Article MeSH List:Adoptive Transfer; Alzheimer Disease(immunology; pathology; therapy); Amyloid beta-Peptides(analysis; genetics; physiology); Animals; Cognition(physiology); Disease Models, Animal; Hippocampus(pathology; physiopathology); Humans; Lymphocyte Transfusion; Mice; Mice, Transgenic; Synapses(pathology); Synaptophysin(analysis); T-Lymphocytes(immunology)
Curation Last Updated:2015-07-30 20:38:20