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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621178
Title:
Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice.
Authors:
Alves, Sandro; Churlaud, Guillaume; Audrain, Mickael; Michaelsen-Preusse, Kristin; Fol, Romain; Souchet, Benoit; Braudeau, Jérôme; Korte, Martin; Klatzmann, David; Cartier, Nathalie
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.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice. 2017, 140 (3):826-842 Brain
Journal:
Brain : a journal of neurology
Issue Date:
1-Mar-2017
URI:
http://hdl.handle.net/10033/621178
DOI:
10.1093/brain/aww330
PubMed ID:
28003243
Type:
Article
Language:
en
ISSN:
1460-2156
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorAlves, Sandroen
dc.contributor.authorChurlaud, Guillaumeen
dc.contributor.authorAudrain, Mickaelen
dc.contributor.authorMichaelsen-Preusse, Kristinen
dc.contributor.authorFol, Romainen
dc.contributor.authorSouchet, Benoiten
dc.contributor.authorBraudeau, Jérômeen
dc.contributor.authorKorte, Martinen
dc.contributor.authorKlatzmann, Daviden
dc.contributor.authorCartier, Nathalieen
dc.date.accessioned2017-11-17T15:20:44Z-
dc.date.available2017-11-17T15:20:44Z-
dc.date.issued2017-03-01-
dc.identifier.citationInterleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice. 2017, 140 (3):826-842 Brainen
dc.identifier.issn1460-2156-
dc.identifier.pmid28003243-
dc.identifier.doi10.1093/brain/aww330-
dc.identifier.urihttp://hdl.handle.net/10033/621178-
dc.description.abstractInterleukin-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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAlzheimer Diseaseen
dc.subject.meshAmyloid beta-Protein Precursoren
dc.subject.meshAnimalsen
dc.subject.meshAntipsychotic Agentsen
dc.subject.meshCase-Control Studiesen
dc.subject.meshDendritic Spinesen
dc.subject.meshDisease Models, Animalen
dc.subject.meshExcitatory Postsynaptic Potentialsen
dc.subject.meshFemaleen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHumansen
dc.subject.meshInterleukin-2en
dc.subject.meshMaleen
dc.subject.meshMemory Disordersen
dc.subject.meshMiceen
dc.subject.meshMice, Transgenicen
dc.subject.meshNeuronal Plasticityen
dc.subject.meshPlaque, Amyloiden
dc.subject.meshPresenilin-1en
dc.subject.meshSynapsesen
dc.titleInterleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalBrain : a journal of neurologyen

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