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

Biomedical Sciences, University of California Riverside, 92521-0121, USA.
Neurobiology of Disease (Impact Factor: 5.08). 09/2006; 23(2):351-61. DOI: 10.1016/j.nbd.2006.03.008
Source: PubMed


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.

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Available from: Chuanhai Cao, Sep 09, 2014
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    • "Many studies have reported the link that exists between the immune system and neurological disease, including AD32333435. Currently, mounting research have focused on immunotherapies and T-cell therapy as major approaches to treating these disorders [7, 8, 36]. It has been suggested that targeting the immune system may be the safer and more effective treatment approach for AD [37, 38]. "
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    • "Immune cells such as dendritic-like microglia, macrophages in CNS, and peripheral T cells, along with cytokines, maintain the proper microenvironment in brains and prevent the development of neurodegenerative diseases by clearing cerebral metabolites and deleterious substances (Cao et al., 2009; Hawkes and McLaurin, 2009; Kipnis et al., 2004; Moalem et al., 1999; Rolls et al., 2007; Ron-Harel et al., 2008; Simard et al., 2006). As Alzheimer's disease (AD) is one kind of neurodegenerative diseases, immunotherapy against AD have been extensively explored in recent years (Cao et al., 2009; Ethell et al., 2006; Fisher et al., 2010; Fuhrmann et al., 2010; Kummer et al., 2012). "
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