Healthy young adults carrying a gene variant that is a major risk factor for the disease seem to have extra activity in brain regions related to memory, even when their brains are at rest.
The gene APOE codes for a protein thought to help create, maintain and repair neuronal connections. One variant, epsilon 4, is considered the biggest risk factor for getting Alzheimer鈥檚, increasing your risk by up to 4 times if you have one copy and up to 12 if you have two. It is not known exactly how epsilon 4 ups the risk, but in people who carry it and have developed Alzheimer鈥檚, the hippocampus, which is involved in memory functions, is usually smaller.
To figure out if epsilon 4 influences brain function earlier on in life, of the University of Oxford and colleagues at Imperial College London scanned the brains of 18 healthy adults with epsilon 4 and 18 controls who did not have the variant. In the scanner, the volunteers spent time performing memory tests and also doing nothing.
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Brain differences
During the memory task, the epsilon 4 carriers had more activity in the hippocampus compared with controls, even though there was no difference in their performance on the tests, suggesting that their hippocampuses expend more energy to achieve the same result.
For the scans when the volunteers did nothing, the researchers focused on the default mode network, a series of connected sites throughout the brain that are active even when the volunteer is resting. Parts of the DMN found in the hippocampus were more active in the at-risk adults than in controls. 鈥淭he fact that we got differences in the hippocampus is very exciting,鈥� says Mackay.
One way to interpret this is that epsilon 4 causes brain regions responsible for memory to get overworked early in life, prompting them to 鈥渂urn out鈥� with age and leading to Alzheimer鈥檚. However, it鈥檚 impossible to tell whether the extra activity contributes to Alzheimer鈥檚 symptoms later on or is just a sign of inefficient brain circuitry in the hippocampus.
鈥楾our de force鈥�
Neurologist of Stanford University, who studies the DMN in people with Alzheimer鈥檚, agrees but says the work is a 鈥渞eal tour de force鈥� because it shows differences so early on. 鈥淭hese subjects are several decades away from the point at which we would expect to pick up on the subtlest signs of cognitive difficulty,鈥� he says.
Mackay says the next step is to look for early differences in brain function between those who have the gene variant and go on to suffer from Alzheimer鈥檚, and those who have it and don鈥檛. Such differences might be used to target interventions at certain people before the disease develops.
Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0811879106)
