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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