Rare genetic discoveries driving breakthroughs for everyone affected by Alzheimer’s


By Ed Pinches | Friday 12 April 2019

Dr Selina Wray, an Alzheimer’s Research UK-funded scientist from University College London, and researchers from the UK Dementia Research Institute (UK DRI) have shed new light on how genetic mutations cause familial Alzheimer’s disease.

Through your support, you have helped to support Dr Wray throughout her career, allowing her to build her expertise, grow her team and emerge as one of the top young scientists working in an exciting area of dementia research.

Now her new findings on how genetic mutations lead to nerve cell changes in familial Alzheimer’s disease (FAD) have been published in the scientific publication Molecular Psychiatry.

A rare genetic form of Alzheimer’s

Familial Alzheimer’s disease is rare. Around the world there are only a few hundred families who have been identified as having faulty genes that cause the disease.

This form of the disease accounts for less than one percent of all Alzheimer’s cases, and people affected by FAD usually start to experience symptoms before the age of 65. For some it is as young as 30.

Researchers like Selina want to better understand what causes the disease so that we can help develop new treatments for those affected.

Familial Alzheimer’s shares many features with the much more common, non-inherited form of the disease. Discoveries in FAD can lead to breakthroughs for everyone affected by Alzheimer’s.

How did they shed more light on familial Alzheimer’s disease?

Dr Wray is a pioneer in using a Nobel prize-winning stem cell technique to research diseases that cause dementia.

Taking skin cells donated by people with a genetic form of Alzheimer’s she turns them into stem cells – cells that have the potential to become any type of cell in the body. Her team then transform these cells into nerve cells similar to those in the brain.

By working with cells donated by people with familial Alzheimer’s, Selina and her team investigated the effect of genetic mutations on the production of amyloid, a protein that builds up in the brain in the disease.

So, what did they find?

In the study Dr Wray shed more light on the genetics underpinning familial cases of Alzheimer’s disease.

Her findings indicate that different mutations in the genes responsible for FAD have different affects. While they all lead to a build-up of amyloid protein, she found that there are potentially four distinct mechanisms that can play a role in the disease.

Researchers at the UK DRI collaborated with Selina in this research. They found that amyloid signatures in samples of spinal fluid of people with FAD matched a similar profile to the nerve cells grown in the dish.

What does this mean?

The molecular events that lead to amyloid build-up are important targets for experimental Alzheimer’s drugs. The differences Selina has identified could guide the development of drugs that are targeted to patients depending on which mechanism is at play in their brain.

Tests of spinal fluid could then potentially indicate if a treatment is having the desired effect, or if a person could benefit from a different dose.

This kind of development is still a long way off. But these new findings are another piece of a very complex and important puzzle. Every bit of new knowledge adds to our understanding of diseases like Alzheimer’s and with your support, researchers like Selina are driving this vital progress.

What do the experts say?

Talking about her findings, Dr Selina Wray, said:
“This work reveals deeper insights into the complex interaction between faulty genes and the proteins implicated in familial Alzheimer’s disease. Understanding the disease pathways that cause dementia in more detail is critical to help design and deliver new treatments that could help slow or stop disease progression.

“Receiving funding from Alzheimer’s Research UK has supported me throughout my career and made this important research possible.”

Dr Carol Routledge, Director of Research at Alzheimer’s Research UK said,
“Familial Alzheimer’s disease can be a devastating diagnosis for someone and for their families and we must find an effective way to treat the condition. This work takes us one step closer in our hunt for a life-changing treatment for dementia but there is much still to do.

“This new paper is testament to Dr Wray’s hard work and it’s great to see her research group collaborate so closely with scientists at the UK Dementia Research Institute. Working in partnership with others will be critical as we continue to drive breakthroughs that change people’s lives.

“We’re delighted and proud to be able to fund a passionate dementia researcher like Selina as she continues work to unravel a process that underlies dementia which causes heartbreak to so many. It’s thanks to you, our dedicated supporters, that we are able to fund ground-breaking dementia research.”

Making breakthroughs possible

There is hope, it rests in the hand’s researchers, like Selina. By supporting them we are able to build-up our understanding of the diseases that cause dementia. This will be critical in making breakthroughs possible for those living with dementia and for their families.

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  1. Terry Gashe on 31st May 2019 at 10:07 pm

    Really interested to read about Familial Alzheimer’s Disease. My wife was diagnosed with Alzheimer’s in2014. Her mother’s brother and sister both had dementia but I don’t know if it was diagnosed as Alzheimer’s..we have two daughters and I would not wish to worry them if she does have FAD unless there would be a significant benefit in doing so. What do you suggest?

  2. Jo Rushton on 20th September 2019 at 1:24 pm

    I was very surprised by the report on FAD.
    My father, his mother and his sister all suffered from dementia that became apparent in their 80s. My father was diagnosed with Alzheimer’s and I believe my aunt was too. My grandmother died in 1967 after several years in a geriatric ward. They all lived well into their 90s.
    Was this just an extraordinary coincidence ? I have had a MRI scan of my brain, aged 80, and no signs of AD were found. My sister says she ‘fully expects’ to develop it.

    • Alzheimer's Research UK on 17th January 2020 at 10:11 am

      Apologies for the delay in getting back to you Jo, I hope you find the following information useful.

      This blog post is covering information for familial Alzheimer’s disease (FAD) which is a rare form of directly inherited Alzheimer’s disease that usually affects people in their 30’s and 40s. FAD is caused by a mutation in a gene which is passed on through every generation of a family, from parents who have developed the condition to their children who then have a 50/50 chance of developing it too.

      In your family’s case, where Alzheimer’s developed later in life, this is most likely caused by a complex mixture of things including age, genes and lifestyle. Like with other diseases, we can inherit risk genes from our parents, the most well-known risk gene for Alzheimer’s disease is called APOE4.

      People with one copy of APOE4 are around three times more likely to be affected, and people with two copies, one copy from each parent, are around eight times more likely to develop Alzheimer’s.

      However, many people who carry APOE4 do not develop Alzheimer’s disease due all the other risk factors involved in its development. Because the risk of Alzheimer’s disease increases as we age, and because of the effects of common genes like APOE4, it is not unheard of for multiple people in the same family to have the condition.

      If your sister is worried she can speak with her GP and explain your family history and any concerns she has. If either of you would like to know more about genes and dementia, you can read more here

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Ed Pinches

Team: Science news