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ID 2136

Amyloid beta causing forgetfulness

Professor Dennis Selkoe discusses an experiment by his group, which found that a-beta oligomers temporarily injected into rats' brains caused temporary forgetfulness.
What we find if we try to extract amyloid beta from Alzheimer’s [disease] patients versus other dementias – they don’t have to be normal controls, any kind of dementia – is that only the Alzheimer’s [disease] patients have an abundance of these small doublets, triplets, quadruplets of amyloid beta or a-beta. People with another kind of dementia called frontotemporal dementia, we’ve extracted those brains and they have almost no soluble a-beta doublets and triplets (dimers and trimers). The same thing with another dementia called Louibody dementia, and people who have had strokes as a cause of dementia, they also have very little. What’s interesting is that some of those patients do have small amounts or modest amounts of amyloid plaques, and the reason is that as they make a little bit too much a-beta, it goes into plaques and gets sequestered, and they generally have less plaques than typical Alzheimer’s [disease] patients. But, the plaques hold onto the a-beta and they don’t have much soluble a-beta floating around in the brain fluid. So the difference between Alzheimer’s [disease] and other conditions is that the doublets and triplets are locked up quite nicely into plaques in these other conditions. In Alzheimer’s [disease] they are also locked up into plaques, but apparently there is such a problem with a-beta production or clearance that the plaques can’t hold them all and the soluble level rises. So, what we did in our research was to extract from different patients’ brains after the patient died and see whether the a-beta doublets and triplets from Alzheimer’s [disease] patients could impair memory. So we’re not allowed to extract it from a patient and inject it back into a healthy person – that’s not ethical. So instead we got permission to inject tiny amounts of it into the fluid-filled space of a rat brain, a living adult rat. We found that as soon as we injected the material from the human brain, the rat became forgetful. It didn’t remember a task that we had taught it to remember, and in that experiment, after a few hours, the a-beta cleared out of the rat brain and the rat was back to normal. So, one of the key findings of our recent research is that small doublets and triplets of a-beta can be harvested or taken out of the brains of people who died with Alzheimer’s [disease] and they can confer the memory abnormality that we know happened in the patient. So this is sort of transmitting the disease process into a simpler animal model.
amyloid plaques, amyloid, beta, a-beta, oligomer, dimer, rat, brain, forgetfulness, dennis, selkoe
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.

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