Woman who is ‘immune to Alzheimer’s’ despite her family being blighted by disease may offer clues to beat dementia

A woman who avoided Alzheimer's despite the disease affecting most of her family may provide clues on how to beat the disease, a study suggests.

The unnamed Colombian woman, now in her late 70s, has remained fit and healthy despite half of her family being affected by the condition, with some even developing it in their 40s.

She carries two copies of a rare variant of the APOE gene, the Christchurch mutation.

In the latest study, researchers at Washington University in St. Louis used genetically modified mice to show that the mutation breaks the link between the early stage of Alzheimer's disease, when amyloid beta builds up in the brain, and the later stage , when tau tangles build up and cognitive decline begins.

They found that the mutation made the brain's waste disposal cells more efficient at removing tau tangles. They found that the mutation made the brain's waste disposal cells more efficient at removing tau tangles.

This means that the woman's brain was still filled with amyloid, but she remained mentally sharp.

Dr. David Holtzman, lead author of the study and professor of neurology, said: 'Each protective factor is very interesting because it gives us new clues about how the disease works.

'As people age, many begin to develop a build-up of amyloid in their brains.

'Initially they remain cognitively normal. However, after many years, the deposition of amyloid begins to lead to the accumulation of the tau protein.

'If this happens, a cognitive disorder quickly develops. If we can find a way to mimic the effects of the APOE Christchurch mutation, we may be able to stop people who are already on the path to Alzheimer's dementia from continuing on that path.”

This could lead to the creation of new drugs that mimic the impact of the mutation and prevent amyloid in people's brains from worsening to Alzheimer's.

Alzheimer's disease builds up over about thirty years, with the first two decades happening silently as amyloid builds up but causing no negative effects.

When amyloid levels reach a tipping point, tau tangles will spread throughout the brain and cause cell death.

The brain slows down and begins to shrink, leading to thinking and memory problems.

Dr. Holtzman said, “One of the biggest unanswered questions in the field of Alzheimer's disease is why amyloid accumulation leads to tau pathology.

“This woman was very, very unusual in that she had amyloid pathology, but not much tau pathology and only very mild late-onset cognitive symptoms. This made us suspect that she might have clues to this link between amyloid and tau.”

The researchers used mice that had been genetically modified to overproduce amyloid and altered them so that they carried the human APOE gene with the Christchurch mutation.

They then injected the mice's brains with a small amount of human tau, which normally caused tau to spread throughout the brain.

However, as with the Colombian woman, the mice developed only a small spread of tau, despite having high levels of amyloid.

The researchers realized that the crucial difference was how active the brain's waste-removal cells called microglia were.

In the mice with the APOE Christchurch mutation, the microglia surrounding amyloid plaques were very efficient at removing tau clusters.

Dr. Holtzman said, “These microglia take up the tau and break it down before the tau pathology can effectively spread to the next cell.”

'That blocked a large part of the downstream process; without tau pathology you don't get neurodegeneration, atrophy and cognitive problems.

'If we can mimic the effect of the mutation, we may be able to make the accumulation of amyloids harmless, or at least much less harmful, and protect people from developing cognitive disorders.'

The research was published in the journal Cell.