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

Active and passive Aβ 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 Aβ-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 Aβ-specific immune cells from Aβ-vaccinated littermates improved performance in cognitively impaired APP + PS1 mice. Recipients had lower levels of soluble Aβ in the hippocampus, less plaque-associated microglia, and more intense synaptophysin immunoreactivity, compared with untreated controls. However, Aβ-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 Aβ can cause immune tolerance, hypo-responsiveness, or anergy to Aβ, but our findings demonstrate that Aβ-specific immune cells can resume endogenous Aβ-lowering processes and may be an effective Aβ therapeutic.