Scientists from the UK's Oxford University and Imperial College London have shown that carriers of a gene variant which increases Alzheimer's risk by up to ten times may have increased brain activity in a key area of the brain, long before symptoms of the disease develop. The research, published in the journal Proceedings of the National Academy of Science, may be an initial step towards the development of a test for predicting those at greatest risk from developing the disease.
It has long been known that one particular version of the APOE gene, known as epsilon 4 (e4), can increase an individual's chance of developing Alzheimer's disease in later life. The variant can increase a person's risk of the disease by up to four times, if one copy is carried, and by up to ten times, if two copies are carried. However, the majority of people who carry the gene variant do not develop the disease, raising the prospect of other genetic and environmental risk factors yet to be discovered. At present, there is no reliable test for predicting which carriers of the APOEe4 gene variant will go on to develop the condition.
The study involved 36 healthy volunteers, aged between 20 and 35, of which 18 carried at least one copy of the APOEe4 gene variant. The volunteers were asked to carry out tests designed to stimulate an area of the brain known as the 'hippocampus', known to be implicated in the formation of long-term memories, and also to do nothing whist having their brain activity measured by an fMRI scanner. The APOEe4 carriers all showed greater activity in the hippocampus, even when idle, leading the researchers to suggest that over-activity may 'wear out' this key area of the brain in APOEe4 carriers who go on to develop Alzheimer's disease.
Dr Clare Mackay from the Department of Psychiatry and the Centre for Functional Magnetic Resonance Imaging of the Brain at the University of Oxford, who led the study, hopes that it could help to identify those at greatest risk from Alzheimer's disease who may benefit from early treatment interventions, lifestyle modifications or regular screening. 'We have shown that brain activity is different in people with this version of the gene decades before any memory problems might develop... These are exciting first steps towards a tantalising prospect: a simple test that will be able to distinguish who will go on to develop Alzheimer's,' she said.
Around one in four people carry at least one copy of the APOEe4 gene variant. Further studies will be needed to confirm whether over-activity of the hippocampus in APOEe4 carriers can accurately predict the development of Alzheimer's disease in this age group.