Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuron. 2015 Feb 4;85(3):519-33. doi: 10.1016/j.neuron.2014.11.020. Epub 2015 Jan 22.

IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior.

Author information

1
Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: pchakrabarty@ufl.edu.
2
Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
3
Institute for Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USA.
4
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
5
Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: tgolde@ufl.edu.

Abstract

Anti-inflammatory strategies are proposed to have beneficial effects in Alzheimer's disease. To explore how anti-inflammatory cytokine signaling affects Aβ pathology, we investigated the effects of adeno-associated virus (AAV2/1)-mediated expression of Interleukin (IL)-10 in the brains of APP transgenic mouse models. IL-10 expression resulted in increased Aβ accumulation and impaired memory in APP mice. A focused transcriptome analysis revealed changes consistent with enhanced IL-10 signaling and increased ApoE expression in IL-10-expressing APP mice. ApoE protein was selectively increased in the plaque-associated insoluble cellular fraction, likely because of direct interaction with aggregated Aβ in the IL-10-expressing APP mice. Ex vivo studies also show that IL-10 and ApoE can individually impair glial Aβ phagocytosis. Our observations that IL-10 has an unexpected negative effect on Aβ proteostasis and cognition in APP mouse models demonstrate the complex interplay between innate immunity and proteostasis in neurodegenerative diseases, an interaction we call immunoproteostasis.

PMID:
25619653
PMCID:
PMC4320003
DOI:
10.1016/j.neuron.2014.11.020
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center