Rogue Alzheimer's gene causes early brain changes

British scientists have found that some young adults who carry a certain genetic variant have an increased risk of developing Alzheimer's disease and distinct brain patterns and changes in their brain activity started decades before any symptoms appeared.

The rogue gene APOE4 appears to alter brain activity throughout life and the researchers suggest their finding might lead to a better test for Alzheimer's risk.

Although the APOE4 genetic variant is found in about a quarter of the population not everyone with the variant will develop Alzheimer's - people who inherit one copy of APOE4 have up to four times the normal risk of developing the late-onset variety of the disease - while people who have two copies have around ten times the normal risk.

The researchers from the University of Oxford and Imperial College London conducted a new brain imaging study and they say the results may support the idea that the brain's memory function may gradually wear itself out in those who eventually develop Alzheimer's.

The research offers clues into why some people develop Alzheimer's disease and may lead to a diagnostic test that identifies individuals at risk. The degenerative condition is the most common cause of dementia and it affects millions of people worldwide.

Other research has shown that there are differences in the region of the brain involved in memory, known as the hippocampus, in middle-aged and elderly healthy carriers of APOE4 but this new research is the first to show hyperactivity in the hippocampus of healthy young carriers and that APOE4 carriers' brains behave differently even at 'rest'.

It seems that people with the APOE4 gene have busier brains than people with other forms of the APOE gene and the researchers say when they did a memory task, the APOE4 carriers had more activity in a part of the brain involved in long-term memory and navigation - which is the first area known to be affected in Alzheimer's disease.

Dr. Christian Beckmann of Imperial College London, says it could be that the brain just wears itself out in some people as even when the volunteers carrying APOE4 weren't being asked to do anything, the memory part of their brain could be seen to be working harder than it was in the other volunteers.

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, says these are the first steps towards a simple test that will be able to distinguish who will go on to develop Alzheimer's.

For the study the researchers used a type of real-time imaging called functional magnetic resonance imaging or fMRI to look at the brains of 36 volunteers aged 20 to 35, 18 who had at least one copy of APOE4 - none of whom were experiencing any memory problems and all performed normally on tasks designed to test their cognitive skills.

The researchers will now carry out a similar study of patients with mild cognitive impairment to explore how these differences in patterns of brain activity in young people may be associated with later changes.

The research is published in the journal Proceedings of the National Academy of Sciences.