Some people are strangely resistant to Alzheimer’s disease. Here’s what sets them apart. : Science Alert

Some people have changes consistent with Alzheimer’s disease without showing any symptoms, almost as if their brains are more resistant to the disease. A new study has explored how this puzzling phenomenon could pave the way for treatments.

A team of researchers led by scientists from the Netherlands Institute of Neuroscience examined brain tissue samples stored at the Netherlands Brain Bank, a repository of donated brains from more than 5,000 people who died of brain disease.

Among these thousands of samples, the team found only 12 that were cognitively healthy before their deaths, but showed clear neurological signs of the disease’s underlying pathology.

Beyond demonstrating how rare it is for brains to escape the debilitating effects of Alzheimer’s disease, the small sample gave the team the opportunity to learn what might make these brains so resilient.

“It’s not clear what’s happening in these people at the molecular and cellular levels,” says Luuk de Vries, a neuroscientist at the Netherlands Institute of Neuroscience. “So we looked for donors with brain tissue abnormalities who did not have cognitive decline in the brain bank.”

This type of resilience has been observed before, and it is thought that the genetics we are born with and the lifestyle choices we make may have some effect. These different factors are also linked to the development of Alzheimer’s disease in general.

By analyzing the unique combinations of hundreds of genes expressed in the brains of cognitively healthy people with Alzheimer’s, in the brains of more typical Alzheimer’s patients, and in healthy controls without the disease, researchers have discovered key differences in resilient brains related to astrocyte cells involved in the removal of waste from the brain.

Additionally, resilient brains seemed better able to eliminate toxic proteins associated with the development of Alzheimer’s disease. It seems that these brains are somehow more effective at preventing the accumulation of neurological waste.

Another difference was more efficient energy production in resilient brain cells. It is not yet clear what lies behind these differences or how they are linked to Alzheimer’s disease, but identifying what these differences are is an important first step.

“If we can find the molecular basis of resilience, then we will have new starting points for the development of drugs that could activate resilience-related processes in Alzheimer’s patients,” says de Vries. .

Alzheimer’s disease now affects an estimated 47 million people worldwide, and that number is growing rapidly. We still don’t know what combination of factors is necessary for degeneration to progress, how to prevent the onset of the disease, or how its damage might be reversed – but each study like this brings us closer to some answers.

The next step in this particular research is to try to understand why there are these differences in the production processes of resilient brains. From there, it might be possible to develop drugs that would help the brain better protect itself.

“It remains difficult to determine from human data which process triggers the disease process,” says de Vries. “You can only demonstrate this by changing something in cells or animal models and seeing what happens next. That’s the first thing we need to do now.”

The research was published in Acta Neuropathology Communications.