According to a new brain imaging study by scientists, young adults with the APOE4 gene variant, which raises their risk of developing Alzheimer's, show changes in their brain activity decades before any symptoms might arise.

The results of the study may support the idea that the brain's memory function may gradually wear itself out in those who go on to develop Alzheimer's.

The research provides clues as to why certain people develop Alzheimer's and it may be a step towards a diagnostic test that identifies individuals at risk.

Alzheimer's is the most common cause of dementia and it affects around 417,000 people in the UK. According to the 2009 Facts & Figures report by the Alzheimer’s Association, as many as 5.3 million people in the United States are living with Alzheimer’s.

The APOE4 genetic variant is found in about a quarter of the population. Not everyone who carries the variant will go on to develop Alzheimer's, but people who inherit one copy of APOE4 have up to four times the normal risk of developing the late-onset variety of the disease. People who have two copies have around ten times the normal risk.of developing Alzheimer's.

The researchers stress that most carriers of APOE4 will not go on to develop Alzheimer's and carriers should not be alarmed by the study's findings.

Differences in the region of the brain involved in memory, known as the hippocampus, have previously been shown in middle-aged and elderly healthy carriers of APOE4. However, the new study is the first to show hyperactivity in the hippocampus of healthy young carriers. It is also the first to show that APOE4 carriers' brains behave differently even at 'rest'.

The study used functional Magnetic Resonance Imaging (fMRI) carried out at the University of Oxford to compare activity inside the brains of 36 volunteers, with 18 carrying at least one copy of the APOE4 gene and 18 non-carriers acting as controls.

All the volunteers in the study were aged between 20 and 35 and all performed normally on tasks designed to test their cognitive skills.

The researchers looked at how the volunteers' brains behaved while they were resting and also while they were performing a memory-related task. Even when the APOE4 carriers were resting, the researchers could see that carriers and non-carriers each had distinct patterns of brain activity. The fMRI scans showed visible differences in how the hippocampus was relating to the rest of the brain.

Dr Clare Mackay, the lead author of the study said: "We have shown that brain activity is different in people with this version of the gene decades before any memory problems might develop. We've also shown that this form of fMRI, where people just lie in the scanner doing nothing, is sensitive enough to pick up these changes. These are exciting first steps towards a tantalizing prospect: a simple test that will be able to distinguish who will go on to develop Alzheimer's."

Dr Christian Beckmann, another author study added: "Our brains are always active - our minds wander even when we're not carrying out specific tasks. We were surprised to see that even when the volunteers carrying APOE4 weren't being asked to do anything, you could see the memory part of the brain working harder than it was in the other volunteers. Not all APOE4 carriers go on to develop Alzheimer's, but it would make sense if in some people, the memory part of the brain effectively becomes exhausted from overwork and this contributes to the disease. This theory is supported by studies that have found the opposite pattern in people who have developed Alzheimer's, with these people showing less activity than normal in the memory part of the brain."

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References:
1. Clare Mackay, et al. Imperial College London.
2. Alzheimer's Association.

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