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.
When we study the effects of a-beta [amyloid beta] oligomers, and weâ€™ve isolated them from human brains from people with Alzheimerâ€™s disease, we can put them onto a brain section of hippocampus from a mouse or a rat, or we can inject them into the brain of a mouse or a rat, and weâ€™ve done both. We can show that they short circuit the hippocampal synapses by interfering with a phenomenon [known as] long-term potentiation or LTP. A-beta oligomers are very potent inhibitors of LTP, and weâ€™ve learned and published recently that they are remarkably potent, that the amount of a-beta oligomers, if you harvest it from a patient who died with Alzheimerâ€™s disease, even if there is a lot of a-beta there, the amount that you need to just interfere with LTP is not a lot, what we call sub-nanomolar quantities. 1x10-9 moles of a-beta, which would be a very small amount, would be more than sufficient to block LTP. Now, LTP is an important correlate of memory and learning, and so we think itâ€™s meaningful that we can take a-beta out of the patientâ€™s brain, study it biochemically, learn that its doublets and triplets and quadruplets floated onto a section of mouse hippocampus and interfere with LTP. In fact, beyond that we can actually induce whatâ€™s called LTD, as in depression, long-term synaptic depression. Oligomers will induce that, which is bad, and theyâ€™ll inhibit long-term potentiation, which is generally viewed as good. Very importantly, we can link those phenomena of LTP and LTD to memory by taking another aliquot or another little helping of the same a-beta we isolated and putting it into an awake adult rat and showing that the rat is forgetful. So, in some ways, thereâ€™s been a debate about whether LTP is unequivocally a reflection of memory symptoms and memory function in humans. We can say that, from our work on Alzheimerâ€™s [disease], there is an excellent correlation. What happens in the Alzheimerâ€™s [disease] patientâ€™s brain that makes them forgetful inhibits LTP in a simpler system and makes a rat forgetful, as well. So we can connect Alzheimerâ€™s [disease] memory loss, a ratâ€™s memory failure with the material from an Alzheimerâ€™s [disease] patient, and inhibition of LTP.
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Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.
Professor Dennis Selkoe discusses the largely linear relationship between a-beta and cell death in the brain.
An overview of Alzheimer's disease-related content on Genes to Cognition Online.
Professor Dennis Selkoe explains that amyloid beta oligomers - small assemblies of amyloid beta protein associated with Alzheimer's disease - do not cause plaques but prevent them.
Professor Dennis Selkoe concludes that neurons are not the only type of cell affected in Alzheimer's disease.
Professor Dennis Selkoe discusses an experiment by his group, which found that a-beta oligomers temporarily injected into rats' brains caused temporary forgetfulness.
Professor Dennis Selkoe discusses the age at which plaque-forming a-beta can begin to build up. Children with Down syndrome may have these plaques, otherwise childhood instances are rare.
Long-term Potentiation of synaptic transmission is commonly referred to as LTP. It can be recorded in many parts of the nervous system, but is very widely studied in the hippocampus.
Professor Dennis Selkoe discusses the degree to which the ApoE4 gene is associated with early onset Alzheimer's disease.
Professor Graham Collingridge describes the process of long-term potentiation (LTP) - the process by which synapses increase their efficiency.