Format

Send to

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

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

Author information

1
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.
2
Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215; hes@bu.edu Elena.Galea@uab.cat wzmorrison@gmail.com.
3
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.

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.

KEYWORDS:

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

PMID:
26644572
PMCID:
PMC4697430
DOI:
10.1073/pnas.1516779112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center