Healthy young people who carry a genetic variant that raises the risk for Alzheimer’s disease show differences in the brain decades before memory problems typically arise, according to research published today in the Proceedings of the National Academy of Sciences. Brain-imaging studies found that carriers had a hyperactive hippocampus, part of the brain central to learning and memory, even when mentally at rest. Scientists involved in the study say that the findings support the idea that the memory part of the brain is overworked in high-risk people, which over time could contribute to the disease.

Researchers used functional magnetic brain imaging to assess brain activity in 36 adults ages 20 to 35, half of whom carried at least one copy of the at-risk variation, and all of whom performed normally on tasks designed to test their cognitive skills. Not everyone who carries the variant, called APOE4, will develop Alzheimer’s. But those who have one copy have a quadrupled risk of the disease, while those with two copies have about ten times the average risk.

According to a press release from Imperial College London,

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 Oxford University and Imperial 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.”

Dr. Christian Beckmann, another author of today’s study from the Division of Neurosciences and Mental Health at Imperial College London, 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.”