A Molecule That Can Improve Memory Function
This article was originally published by the BHRC [http://www.otago.ac.nz/bhrc/news/otago629706.html]
Dementia is one of the fastest growing health issues facing countries throughout the world. As the average age of populations increases dementia becomes a greater problem for individuals and their families, and so researchers the world over are trying to find ways of maintaining a high quality of life through the older years.
A team of researchers, led by Professors Cliff Abraham and Warren Tate, have recently investigated a protein which may help - soluble amyloid precursor protein-alpha (sAPPα). This protein shows great promise in improving some forms of memory, but this effect may be most helpful for individuals who are already experiencing cognitive problems.
The word ‘amyloid’ may be familiar to you. It comes up very often in discussions about Alzheimer’s disease. In Alzheimer’s disease there is a build-up of amyloid-beta between brain cells. This amyloid-beta clumps together eventually forming insoluble masses called plaques that damage brain cells and make it difficult for them to communicate. A loss of communication causes a loss of function and, along with a number of other pathologies, results in the cognitive decline that is the hallmark of Alzheimer’s disease.
Your brain cells create amyloid-beta by cutting up a protein, called amyloid-precursor protein, using specific kinds of molecular scissors. Once it is cut, it separates into several pieces – one cutting pathway creates amyloid-beta and another longer fragment called soluble amyloid precursor protein-beta (sAPPβ). If, however, neural cells use a different pathway and different molecular scissors then the toxic amyloid beta can’t be produced and a different fragment is snipped off, soluble amyloid precursor protein-alpha (sAPPα). The difference between sAPPα and sAPPβ is just 16 amino acids, 16 small building blocks that completely change what these proteins do. While sAPPβ has little effect on memory, sAPPα can enhance it especially under conditions when memory is impaired.
In an article recently published in the journal Neurobiology of Learning and Memory, the researchers tested the effect of sAPPα on the spatial memory of lab rats in a test of memory for object location, and a form of molecular memory at nerve cell synapses called long-term potentiation.
They found that, as expected, younger rats tended to outperform older rats. However, after being given sAPPα, the older rats became just as capable of retaining their memories of objects as the younger rats. The researcher saw the same effect on long-term potentiation, a key molecular mechanism underpinning learning and memory. However in a different spatial memory task, the animals responded differently. The older rats’ spatial memory didn’t improve after being given sAPPα, while the younger rats who had been given sAPPα got worse. This demonstrated that sAPPα is not a general purpose cognitive enhancer, and that it may only be helpful to those who are experiencing memory problems in particular ways.
This means that, if it were available on the market, not everyone would necessarily benefit from taking sAPPα. Thus prescriptions would need to be tailored specifically for those with memory problems associated with ageing, and perhaps neurological disorders such as head-injury, stroke or Alzheimer’s disease.
Clearly this work, while far from being available in the clinic, is one of many steps being taken to identify potential ways to rescue the brain from age-related cognitive decline. With time such studies will become even more important, and we hope that further testing with active fragments of sAPPα will lead to a potential treatment for a wide range of cognitive impairments.