Amyloid Goes Global

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Sci. Signal.  24 Mar 2009:
Vol. 2, Issue 63, pp. pe16
DOI: 10.1126/scisignal.263pe16

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The brains of patients with Alzheimer’s disease (AD) contain abundant plaques composed of β-amyloid (Aβ) peptides. It has been assumed that amyloid plaques and soluble Aβ oligomers induce neuronal pathology in AD; however, the mechanism by which amyloid mediates pathological effects is not clearly understood. In vivo calcium (Ca2+) imaging and array tomography studies with AD mouse models are providing new insights into the changes that occur in brain structure and function as a result of amyloid plaque accumulation. The unexpected lesson from these studies is that amyloid plaques result in both localized and global changes in brain function. The amyloid-induced effects include short-range changes in neuronal Ca2+ concentrations, medium-range changes in neuronal activity and synaptic density, and long-range changes in Ca2+ signaling in astrocytes and induction of intracellular Ca2+ waves spreading through a network of astrocytes. These results have potential implications for understanding synaptic and neuronal network dysfunction in AD brains.

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