By Michael Slezak
It’s one of the biggest mysteries of Alzheimer’s. The disease is associated with the formation of protein plaques in the brain, but why is it that some people with plaques seem not to have the disease?
Research suggests that some people’s brains are able to reorganise during the early stages of Alzheimer’s, delaying the appearance of initial symptoms.
The plaques in question are small mounds of a protein called beta-amyloid, and are found in the brains of people with Alzheimer’s disease. Whether these plaques are a cause of the disease has been hotly debated. One reason for doubt is the appearance of plaques in many older people who have no symptoms Movie Cameraof dementia at all.
Using fMRI to measure changes in blood flow around the brain, William Jagust from the University of California in Berkeley and colleagues compared brain function in three groups of people without symptoms of dementia: 22 young people, 16 older people with beta-amyloid plaques and 33 older people without the plaques. He asked each of them to memorise a photographed scene while inside the machine.
Jagust found that older people with plaques had increased blood flow – which means stronger activation of that brain area – in the regions of the brain that are usually activated during memory formation, compared with the older people who did not have plaques. The team then analysed whether this extra brain activation might be helping to compensate for the plaques.
Fifteen minutes after the scanning and memory task, the team presented the participants with six written details about the scenes, and asked them whether they were true or false. “We can relate the pattern of activity to the amount of detail they remember from the picture,” Jagust says. “If you do that for 100 or 150 pictures, you get a global sense of how brain activity relates to the richness of the memory or the amount of detail of the memory.”
And the results were clear. In the case of the older people with beta-amyloid, the more accurate their memory of the picture, the more active their brain had been when they studied the image in the fMRI. “That suggested to us that they were able to ramp up activity to retain more information,” says Jagust. “We interpret this as a compensation or plasticity. The older people who didn’t have amyloid in the brain did not do it.”
This boosting of brain activity seems to be related to the amount of plaques a person had. The more beta-amyloid protein someone had, the more they tended to ramp up their brain activity while memorising the scene. However, this effect tailed off in the people with the greatest amount of plaques. “It suggests this is a transitory phenomenon. Eventually, this sort of compensation becomes lost. And that might be something that happens in the progression to cognitive decline,” Jagust says.
Business as usual
The results could also help explain why some people have the plaques without appearing to have dementia. “The fact that brain amyloid is detectable in cognitively normal elderly subjects has been used historically as an argument to support the idea that amyloid may not be as toxic as suggested by experimental studies,” says Roger Nitsch, a neuroscientist at the University of Zurich in Switzerland. “This work challenges this view by addressing how elderly subjects can retain normal cognition despite the presence of brain amyloid.”
Ideally, people with Alzheimer’s would take the test next, to see whether their brain activity also increases, or if they are unable to compensate for the plaques once the disease has progressed. However, it is harder to study people with cognitive problems because the task might prove too difficult to complete.