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[2017] 4월 27일 발표논문입니다.
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   https://academic.oup.com/brain/article/140/3/826/2726614/Interleukin-2… [683]
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 (2017) 140 (3): 826-842. DOI: https://doi.org/10.1093/brain/aww330

Published: 20 December 2016

Abstract
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.