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Science 323 (5918): 1211-1215

Copyright © 2009 by the American Association for the Advancement of Science

Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice

Kishore V. Kuchibhotla,1,2 Carli R. Lattarulo,1 Bradley T. Hyman,1 Brian J. Bacskai1*

Abstract: Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-β plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-β deposits, there exists a more general astrocyte-based network response to focal pathology.

1 Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.
2 Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.

* To whom correspondence should be addressed. E-mail: bbacskai{at}partners.org


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