Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice.

Sandro Alves, Guillaume Churlaud, Mickael Audrain, Kristin Michaelsen-Preusse, Romain Fol, Benoit Souchet, Jérôme Braudeau, Martin Korte, David Klatzmann, Nathalie Cartier

Brain : a journal of neurology 2017 Mar 01

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Interleukin-2 (IL-2)-deficient mice have cytoarchitectural hippocampal modifications and impaired learning and memory ability reminiscent of Alzheimer's disease. IL-2 stimulates regulatory T cells whose role is to control inflammation. As neuroinflammation contributes to neurodegeneration, we investigated IL-2 in Alzheimer's disease. Therefore, we investigated IL-2 levels in hippocampal biopsies of patients with Alzheimer's disease relative to age-matched control individuals. We then treated APP/PS1ΔE9 mice having established Alzheimer's disease with IL-2 for 5 months using single administration of an AAV-IL-2 vector. We first found decreased IL-2 levels in hippocampal biopsies of patients with Alzheimer's disease. In mice, IL-2-induced systemic and brain regulatory T cells expansion and activation. In the hippocampus, IL-2 induced astrocytic activation and recruitment of astrocytes around amyloid plaques, decreased amyloid-β42/40 ratio and amyloid plaque load, improved synaptic plasticity and significantly rescued spine density. Of note, this tissue remodelling was associated with recovery of memory deficits, as assessed in the Morris water maze task. Altogether, our data strongly suggest that IL-2 can alleviate Alzheimer's disease hallmarks in APP/PS1ΔE9 mice with established pathology. Therefore, this should prompt the investigation of low-dose IL-2 in Alzheimer's disease and other neuroinflammatory/neurodegenerative disorders. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Citation

Sandro Alves, Guillaume Churlaud, Mickael Audrain, Kristin Michaelsen-Preusse, Romain Fol, Benoit Souchet, Jérôme Braudeau, Martin Korte, David Klatzmann, Nathalie Cartier. Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice. Brain : a journal of neurology. 2017 Mar 01;140(3):826-842