Scientists have discovered a woman whose brain is ‘remarkably resistant’ to Alzheimer’s because of a genetic mutation.
The unidentified woman, who is in her 70s, is part of an extended family in Colombia whose genes cause them to develop the disease in their 40s.
But she has stayed healthy for an extra 30 years and counting – and doctors say it’s because of one specific mutation in her DNA.
Understanding how the mutation works and how it protects her from the devastating disease could one day lead to new treatments, they said.
Alzheimer’s disease causes around two thirds of cases of dementia and is triggered by the build-up of protein clumps called plaques, which interrupt and destroy nerve cells in the brain and prevent it from functioning normally (illustrated)
Researchers led by Harvard University found the woman when they were studying around 1,200 people from a community in Colombia.
Many of the group have a DNA mutation which makes it almost certain that they will develop Alzheimer’s, and many of them start to show signs in their 40s.
They are an extended family of around 6,000 members who live in and around the city of Medellín and for whom early-onset Alzheimer’s runs in the family.
This one woman, however, remained disease-free into her 70s despite having the same mutation.
And when the scientists scanned her brain, they found she had very high levels of what are called plaques – the clumps of protein which clog up the nerve cells.
These are a hallmark of Alzheimer’s but, despite the growth of them in her brain, the woman did not show any signs of the illness.
‘This is a rare example where the study of just one person could change the thinking of a whole research field,’ said Dr Fiona Carragher, chief research officer at the British charity Alzheimer’s Society, which was not involved in the research.
‘This woman should have developed Alzheimer’s in her 40s, but despite a really high number of amyloid plaques in her brain, she has reached 70 and is still living dementia free.’
After seven decades the woman still only has what is called ‘mild cognitive impairment’, a slowing down of the brain slightly worse than normal ageing.
The Harvard scientists pinned this remarkable survival on a variation they found on a gene named APOE in the woman’s DNA – they called the mutation APOE3 Churchill.
A gene mutation called presenilin 1 (PSEN1) is the one responsible for the early-onset Alzheimer’s disease which is passed on through the Colombian family.
But this woman was the only one in the study observed to have the APOE3 mutation, the scientists wrote in the journal Nature Medicine, and it appeared to cancel out the deadly PSEN1 change.
And the fact that she already had the plaque build-up which usually triggers Alzheimer’s suggests a therapy based on this gene could stop Alzheimer’s which had already started.
Dr Carragher added: ‘This breakthrough opens up a new and promising avenue of Alzheimer’s research although further studies with larger numbers are needed.
‘We need to understand more about how this protective gene mutation is working to make the brain more resilient to amyloid plaques.
‘The hope is that this exciting scientific advance could lead to new treatments and take us a step closer towards a cure for dementia.’
Alzheimer’s disease causes around two thirds of all cases of dementia.
Some 520,000 people in the UK have Alzheimer’s along with 5.8million Americans.
The condition causes progressive brain damage and makes people lose their memory, physical strength, thinking power and emotional control.
An extended family of people from the Antioquia region of Colombia, which contains the city of Medellín, are known to have a DNA mutation which means they pass on early-onset Alzheimer’s disease from generation to generation
Dr Joseph Arboleda-Velasquez, a professor at Harvard Medical School, was among the researchers who led the study.
In experiments they came up with a theory that the APOE3 mutation stopped the gene from binding to a particular sugar known to be linked to Alzheimer’s.
This meant the process by which disease begins could not go ahead as normal which, they wrote, ‘limits neurodegeneration’.
In the paper, Dr Arboleda-Velasquez and colleagues wrote: ‘Our findings have implications for the role of APOE in the… treatment and prevention of Alzheimer’s disease.’
A senior expert at the UK Dementia Research Institute, Professor Tara Spires-Jones, said: ‘As the authors point out, this study of a single person is not sufficient to be certain that the APOE variant was the protective factor.
‘At this stage I would say this is a potential protective gene that will certainly launch exciting new research but needs much more work to confirm.’