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

Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15556-61. doi: 10.1073/pnas.1516779112. Epub 2015 Dec 7.


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.

Keywords: Alzheimer’s disease; astrocyte; spatial analysis; sulforhodamine 101; two-photon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Astrocytes / pathology
  • Astrocytes / physiology*
  • Biophysical Phenomena
  • Cell Movement
  • Computer Simulation
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Models, Neurological
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • PSEN1 protein, human
  • Presenilin-1
  • Recombinant Proteins