Topological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques

Elena Galea, Will Morrison, Eloise Hudry, Michal Arbel-Ornath, Brian J. Bacskai, Teresa Gómez-Isla, H. Eugene Stanley, Bradley T. Hyman

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20 Citations (Scopus)

Abstract

Although the clustering of GFAP immunopositive astrocytes around amyloid-β plaques in Alzheimer's disease has led to the widespread assumption that plaques attract astrocytes, recent studies suggest that astrocytes stay put in injury. Here we reexamine astrocyte migration to plaques, using quantitative spatial analysis and computer modeling to investigate the topology of astrocytes in 3D images obtained by two-photon microscopy of living APP/PS1 mice and WT littermates. In WT mice, cortical astrocyte topology fits a model in which a liquid of hard spheres exclude each other in a confined space. Plaques do not disturb this arrangement except at very large plaque loads, but, locally, cause subtle outward shifts of the astrocytes located in three tiers around plaques. These data suggest that astrocytes respond to plaque-induced neuropil injury primarily by changing phenotype, and hence function, rather than location.
Original languageEnglish
Pages (from-to)15556-15561
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number51
DOIs
Publication statusPublished - 22 Dec 2015

Keywords

  • Alzheimer's disease
  • Astrocyte
  • Spatial analysis
  • Sulforhodamine 101
  • Two-photon

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