Website Search
ID 2141

Glutamate uptake decreased in Alzheimer's disease

Description:
Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.
Transcript:
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.
Keywords:
alzheimer, glutamate, receptor, nmda, ampa, ltp, ltd, long, term, potentiation, depression, dennis, selkoe
Downloads:
Creative Commons License This work by Cold Spring Harbor Laboratory is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

Related content:

1101. AMPA and NMDA Receptors
Professor Graham Collingridge describes the roles played by NMDA and AMPA receptors in long-term potentiation (LTP).
2140. Cells - a-beta inhibits long-term potentiation
Professor Dennis Selkoe notes amyloid beta oligomers are very potent inhibitors of long-term potentiation (LTP) and can 'short circuit' synapses in the hippocampus.
1100. Glutamate Receptors
Professor Graham Collingridge describes the glutamate receptor, AMPA, the workhorse receptor for communicating information.
811. The Glutamate System
Professor Trevor Robbins describes some of the key functions of the excitatory glutamate system, which is integral to information processing and long-term potentiation.
1109. NMDA Receptors, Multi-protein Complexes, & LTP
Professor Tom O'Dell describes the role played by NMDA receptors, as part of a large multi-protein complex, in facilitating long-term potentiation (LTP).
1734. NR1/A0001
NR1 is the obligatory subunit of NMDA receptors.
1789. RAP2A/A0033
Ras-related protein 2A, also known as RAP2A or A0033, belongs to the class of G proteins and has been shown to be important in the regulation of both long-term potentiation (LTP) and LDP.
1107. Depotentiation
Professor Tom O'Dell defines depotentiation - the erasure of long-term potentiation (LTP) at the synapse.
1099. Long-term Depression
Professor Graham Collingridge describes the process of long-term depression (LTD), a way of decreasing the efficiency of synaptic transmission.
1997. Learning and memory
Learning and memory are two intimately linked cognitive processes that stem from interactions with the environment (experience).
Cold Spring Harbor Laboratory
CSHL HomeAbout CSHLResearchEducationPublic EventsNewsstandPartner With UsGiving