Secret behind why Alzheimer’s patients cannot make new memories discovered
Scientists discover molecule that stops new memories forming in people with Alzheimer's disease, raising hopes of new drugs to treat dementia
A drug to prevent the devastating memory loss associated with Alzheimer's disease is a step closer after scientists discovered the secret behind why people with dementia cannot form new memories.
It was previously thought that Alzheimer's was primarily caused by the build up of sticky amyloid plaques in the brain which stop neurons from firing.
But drugs to clear the plaques have so far failed to bring any improvement to sufferers.
Many scientists believe that the amyloid plaques trigger a 'cascade effect' of other symptoms meaning that by the time they are spotted it is already too late.
Researchers at Penn State University have now discovered that those plaques may be triggering overproduction of a chemical that drives memory loss by preventing a key part of the brain from functioning.
They believe a drug which targets the chemical – known as GABA neurotransmitter – to prevent it from acting could halt memory loss in sufferers.
"Billions of dollars were invested in years of research leading up to the clinical trials of those Alzheimer's drugs, but they failed the test after they unexpectedly worsened the patients' symptoms," said Professor Gong Chen, a biologist who led the work at Penn State University.
"The research behind those drugs had targeted the long-recognised feature of Alzheimer's brains: the sticky build-up of the amyloid protein known as plaques, which can cause neurons in the brain to die.
"The research of our lab and others now has focused on finding new drug targets and on developing new approaches for diagnosing and treating Alzheimer's disease."
Chen's team found that the GABA neurotransmitter was drastically increased in the deformed versions of the normally large, star-shaped "astrocyte" cells which, in a healthy individual, surround and support individual neurons in the brain.
Those deformed cells were found in the dentate gyrus, a gateway to hippocampus area of the brain that is critical for learning and memory.
The team found that in mice with too much GABA neurotransmitter the neurons in the dentate gyrus are not fired up like they normally would be when a healthy person is learning something new or remembering something already learned.
"We recently discovered an abnormally high concentration of one inhibitory neurotransmitter in the brains of deceased Alzheimer's patients," said Chen.
"After we inhibited the (chemical) in the brains of the mice, we found that they showed better memory capability than the control mice with Alzheimer's disease.
"We are very excited and encouraged by this result, because it might explain why previous clinical trials failed by targeting amyloid plaques alone.
"An ultimate successful therapy may be a cocktail of compounds acting on several drug targets simultaneously."
The discovery also has potential for the development of a new test for Alzheimer's disease, which is the most common form of dementia and one for which no cure has yet been found.
Dr Alison Cook, director of external affairs at the Alzheimer's Association said: ‘We have all felt disappointed by the failure of previous drug trials for Alzheimer’s disease targeting amyloid plaques in the brain.
"This study looks at the potential for tackling one of the changes caused by amyloid plaques as an alternative route to treatment.
"Blocking chemicals in the brain which cause memory loss is an important avenue to explore, but it is only part of what is likely to be a very complicated picture.
Alzheimer’s Society currently funds several projects in this area and believes it to have good potential to find new treatments for the 800,000 people living with dementia in the UK."
The research was published in Nature Communications.
Sarah Knapton - telegraph.co.uk
