“An injection that may stop Alzheimer’s in its early stages has been developed by scientists,” reported the Daily Mail.
This news story is based on an animal study that looked at the process by which genes were switched on during memory formation and how this was affected by amyloid beta, a protein that accumulates in Alzheimer’s disease. The protein has been shown to affect neurone activity, memory and to cause neurones to die in the brain.
The researchers found that another protein called CREB, which is activated when neurones are active, was less active in a mouse model of Alzheimer’s disease. When they injected the mice’s brains with a gene that would increase the activity of CREB, the mice were better able to perform memory tasks.
This research furthers our knowledge of memory processes in an Alzheimer’s disease mouse model; however, the direct relevance to humans is currently limited. The research is not sufficiently advanced yet to call the treatment an Alzheimer’s ‘jab’.
The study was carried out by researchers from The University of Texas in the US. Funding was provided by The US National Institute of Aging. The study was published in the peer-reviewed journal: Proceedings of the National Academy of Sciences.
The Daily Mail briefly covered this research. The implication that scientists have developed an injection that might stop Alzheimer’s in its early stages may lead people to think that this line of research is more advanced than it actually is. An injection of a gene into the brain of a mouse with an Alzheimer’s-like disease is clearly far removed from a therapeutic option for humans with the actual condition.
This laboratory based research investigated whether genes involved in memory are affected in Alzheimer’s disease. When neurones (nerve cells that carry information as tiny electrical signals) are activated, as well as passing messages to the next neurone, they also switch on several genes. These genes produce proteins that strengthen the connections (synapses) between particular neurones. This means that the messages will pass more efficiently between neurones that have previously been active. One of the key proteins that regulate this process is called CREB. When neurones are active, CREB is converted to an active form called CREB-P. CREB-P activity is also dependent on another protein called the CREB-binding protein (CBP) which binds to CREB-P. Together these proteins switch on the genes needed to strengthen the neurone connections.
One theory for the cause of memory loss in Alzheimer’s disease is the accumulation of a protein called amyloid beta. Amyloid beta protein limits neurones passing signals between each other and can cause them to die.
The researchers wanted to see whether CREB activity was affected by amyloid beta. They also wanted to see whether altering the activity of CREB, by changing the levels of CBP, could improve learning and memory in adult mice.
The researchers used a genetically modified model of Alzheimer’s disease in mice. These mice accumulate amyloid beta in their brain and had impaired memory.
The researchers measured the amount of active CREB in the brains of control mice and these ‘Alzheimer’s mice’. The mice were trained in spatial memory tasks for three or five days when they were six months old. This involved training the mice to find their way through a water maze. After this training period, the researchers repeated the measurements of CREB activity.
Alzheimer’s mice had 40% less of an active form of the CREB protein in the area of the brain involved with spatial memory (the hippocampus) than control mice.
In the control mice, the active form of the CREB protein (CREB-P) increased with memory training; however, in the Alzheimer’s mouse the amount of active CREB-P did not increase significantly with training. After five days of training, Alzheimer’s mice had about 200 times less active CREB-P compared to the control mice.
The researchers reduced the amount of amyloid beta in the Alzheimer’s mice by injecting anti-amyloid beta antibodies into their brains. They then measured the amount of CREB-P in these mice and found that Alzheimer’s mice with lower amyloid beta had greater amounts of CREB-P than Alzheimer’s mice that had not received the antibody injection.
The researchers then sought to enhance CREB activity by injecting the mice’s brains with a gene for the CREB-binding protein (CBP). CBP must bind to the CREB protein for it to switch on genes.
Alzheimer’s mice injected with the CBP gene had improved memory performance after seven days compared with Alzheimer’s mice not given the injection.
Despite this improvement in memory however, the injection of the CRB gene had no affect on amyloid beta levels in the mice brains, indicating that restoration of CREB activity alone was sufficient to improve memory.
The researchers said that memory impairment in Alzheimer’s disease can be restored without affecting amyloid beta levels in the brain. They say their data ‘lends support to the use of gene transfer into adult brains as a potential therapeutic approach for Alzheimer’s disease and other related neurodegenerative disorders’.
This preliminary research demonstrated the importance of CREB activity in learning and memory and how this is impaired in a mouse model of Alzheimer’s disease. The researchers showed that injecting mice brains with the gene to make another protein that could restore CREB activity, improved the mice’s performance on memory tasks.
These are promising findings; however, it should be pointed out this is an animal study and its direct relevance to humans is limited. The researchers say their findings support the idea that gene transfer to adult brains can be used as a therapy for Alzheimer’s disease. But as this technique involved the genes being injected directly into the mouse’s brains, further work is required to assess whether a more appropriate delivery method can be used for humans.
Amyloid beta has been associated with directly affecting how neurones pass on signals between each other, and also causing neurone death, both of which would contribute to memory loss in Alzheimer’s disease. The research did not establish whether enhancing neurone activity could prevent the neurone death that would normally occur in Alzheimer’s disease.
This was well-conducted early research, advancing our knowledge of memory impairment in Alzheimer’s disease.