title: Topological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques.
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.
authors.affiliation: Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain; Institut de Neurociències i Unitat de Bioquímica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; hes@bu.edu Elena.Galea@uab.cat wzmorrison@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Galea
authors.affiliation: Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215; hes@bu.edu Elena.Galea@uab.cat wzmorrison@gmail.com.
authors.forename: Will
authors.initials: W
authors.lastname: Morrison
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Eloise
authors.initials: E
authors.lastname: Hudry
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Michal
authors.initials: M
authors.lastname: Arbel-Ornath
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez-Isla
authors.affiliation: Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215; hes@bu.edu Elena.Galea@uab.cat wzmorrison@gmail.com.
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Stanley
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D055592:Biophysical Phenomena; D002465:Cell Movement; D003198:Computer Simulation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D008959:Models, Neurological; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011994:Recombinant Proteins
keywords: Alzheimer’s disease; astrocyte; spatial analysis; sulforhodamine 101; two-photon