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

Abstract

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.

Keywords

• Alzheimer's disease
• Adoptive transfer
• Beta-amyloid
• Cognitive impairment
• Immunotherapy