Glutamate uptake decreased in Alzheimer's disease

Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.

We are now studying the way that human a-beta [amyloid beta] doublets and triplets from an Alzheimer’s [disease] patient block LTP [long-term potentiation] or enhance the phenomenon of long-term depression of synapses, which is not good. What we’ve learned is that a-beta seems to decrease the uptake of glutamate by synapses, so there is too much glutamate in the extracellular space outside the synaptic terminal, and we don’t know exactly how a-beta builds up glutamate on the outside, but we know that glutamate then affects NMDA receptors, which are receptors for glutamate. So, indeed, we believe that small amounts of a-beta, and it’s very potent at these sub-nanomolar concentrations, interferes with proper NMDA receptor function. Now I cannot tell you that it’s only NMDA receptors; other kinds of excitatory amino acid receptors like AMPA receptors and metabotropic glutamate receptors are already likely to be involved, we already have evidence for the so-called mGluR receptors. So NMDA [receptors] are very important, mGluR receptors are very important and probably before that, upstream of that, the mechanism for transporting glutamate into the cell (the glutamate transporter) is adversely impacted by a-beta oligomers.

alzheimer, glutamate, receptor, nmda, ampa, ltp, ltd, long, term, potentiation, depression, dennis, selkoe

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