Editors' ChoiceAlzheimer's Disease

Don't Forget Your Glia

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Science Translational Medicine  24 Mar 2010:
Vol. 2, Issue 24, pp. 24ec48
DOI: 10.1126/scitranslmed.3001077

Much has been published about neuron destruction in Alzheimer’s disease, a self-stealing condition with no cure. The disease pathophysiology implicates a peptide known as amyloid-β (Aβ), which accumulates in the brain and exerts a range of toxic effects on neurons. However, it remains uncertain what effects Aβ may have on astrocytes—glial (nonneuronal) cells in the brain that play crucial roles in brain energy metabolism, defense against neuronal oxidative damage, and regulation of neurotransmitter cycling, each of which is altered in Alzheimer’s disease. Allaman and colleagues now report that Aβ alters astrocyte metabolism in a way that impairs neuron viability.

The authors exposed cultured astrocytes from the cerebral cortex of mice to Aβ peptide fragments and detected increased glucose uptake in these cells, which correlated with cellular internalization of the Aβ peptide and was dependent on a variety of other paramenters: (i) extracellular Aβ aggregation, (ii) the presence of type A scavenger receptors on astrocyte cell membranes, and (iii) activity of the intracellular phosphoinositide 3-kinase (PI3) pathway. Aβ exposure also increased various glucose-related metabolic processes in astrocytes, including lactate and glutathione release into the extracellular space, glycogen storage, and toxic hydrogen peroxide production. When neurons were co-cultured with astrocytes that had been preexposed to Aβ, neuron viability fell—an effect that was similarly influenced by the action of type A scavenger receptors and PI3 pathway activity in astrocytes. These findings suggest that Aβ-induced neuron loss may result in part from altered astrocytes’ metabolism. Although the memory disorder with the highest public health impact still awaits a true breakthrough in treatment, perhaps the cell types once thought to be bystanders in the brain will not be forgotten as potential treatment targets.

I. Allaman et al., Amyloid-β aggregates cause alterations of astrocytic metabolic phenotype: Impact on neuronal viability. J. Neuroscience 30, 3326–3338 (2010). [Abstract]

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