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

Active and passive A beta 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 A beta-specific immune re-activation can provide cognitive and pathological benefits to APPsw + PSI transgenic mice for at least 2 1/2 months. A single infusion of A beta-specific immune cells from A beta-vaccinated littermates improved performance in cognitively impaired APP + PSI mice. Recipients had lower levels of soluble A beta in the hippocampus, less plaque-associated microglia, and more intense synaptophysin immunoreactivity, compared with untreated controls. However, A beta-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 A beta can cause immune tolerance, hypo-responsiveness, or anergy to A, but our findings demonstrate that A-specific immune cells can resume endogenous A beta-lowering processes and may be an effective A therapeutic. (c) 2006 Elsevier Inc. All rights reserved.