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      Transcriptional profiling of CD11c-positive microglia accumulating around amyloid plaques in a mouse model for Alzheimer's disease.

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          Abstract

          Amyloid plaques in Alzheimer's disease (AD) mice are surrounded by activated microglia. The functional role of microglia activation in AD is not well understood; both detrimental and beneficial effects on AD progression have been reported. Here we show that the population of activated microglia in the cortex of the APPswe/PS1dE9 mouse AD model is divided into a CD11c-positive and a CD11c-negative subpopulation. Cd11c transcript levels and number of CD11c-positive microglia increase sharply when plaques start to occur and both parameters continue to rise in parallel with the age-related increasing plaque load. CD11c cells are localized near plaques at all stages of the disease development and constitute 23% of all activated microglia. No differences between these two populations were found in terms of proliferation, immunostaining intensity of Iba1, MHC class II, CD45, or immunoproteasome subunit LMP7/β5i. Comparison of the transcriptome of isolated CD11c-positive and CD11c-negative microglia from the cortex of aged APPswe/PS1dE9 with WT microglia showed that gene expression changes had a similar general pattern. However, a differential expression was found for genes involved in immune signaling (Il6, S100a8/Mrp8, S100a9/Mrp14, Spp1, Igf1), lysosome activation, and carbohydrate- and cholesterol/lipid-metabolism (Apoe). In addition, the increased expression of Gpnmb/DC-HIL, Tm7sf4/DC-STAMP, and Gp49a/Lilrb4, suggests a suppressive/tolerizing influence of CD11c cells. We show that amyloid plaques in the APP/PS1 model are associated with two distinct populations of activated microglia: CD11c-positive and CD11c-negative cells. Our findings imply that CD11c-positive microglia can potentially counteract amyloid deposition via increased Aβ-uptake and degradation, and by containing the inflammatory response.

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          Author and article information

          Journal
          Biochim. Biophys. Acta
          Biochimica et biophysica acta
          Elsevier BV
          0006-3002
          0006-3002
          Oct 2016
          : 1862
          : 10
          Affiliations
          [1 ] Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. Electronic address: w.kamphuis@nin.knaw.nl.
          [2 ] Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands.
          [3 ] Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
          [4 ] Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
          [5 ] Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
          Article
          S0925-4439(16)30167-3
          10.1016/j.bbadis.2016.07.007
          27425031
          034a83a8-a2cb-4991-a799-a1719fdb6c24
          History

          Gene expression,Inflammation,Microglia,,CD11C,CD11b
          Gene expression, Inflammation, Microglia, , CD11C, CD11b

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