Amyloid β-peptide inhibits Na⁺-dependent glutamate uptake

The purpose of this review is to summarize much of the work on the inhibition of the astroglial glutamate transporter in relation to excitotoxic neurodegeneration, in particular, inhibition of uptake by the β-amyloid peptide (Aβ) found in the Alzheimer's disease (AD) brain. There is evidence for oxidative stress in the AD brain, and Aβ has been found to generate reactive oxygen species (ROS), thus adding to the stress or possibly initiating it. The oxidative inhibition of the glutamate transporter protein by Aβ increases the vulnerability of glutamatergic neurons, and by rendering them susceptible to the excitotoxic insult that results from impaired glutamate uptake, Aβ can be directly connected to the neurodegeneration that follows.