TY - JOUR T1 - Amyloid-β<sub>1–42</sub> Slows Clearance of Synaptically Released Glutamate by Mislocalizing Astrocytic GLT-1 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5312 LP - 5318 DO - 10.1523/JNEUROSCI.5274-12.2013 VL - 33 IS - 12 AU - Annalisa Scimemi AU - James S. Meabon AU - Randall L. Woltjer AU - Jane M. Sullivan AU - Jeffrey S. Diamond AU - David G. Cook Y1 - 2013/03/20 UR - http://www.jneurosci.org/content/33/12/5312.abstract N2 - GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-β peptide Aβ1–42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease. ER -