The Jennings vs Alzheimer’s: Shaping a new “treatment era” through discovery

Scribbling the number 23 at the top of the page, Professor Sir John Hardy had no idea that the handwritten letter he’d just reviewed would change the course of Alzheimer’s research forever.

While working at St Mary’s Hospital in 1986, Professor Hardy and his team, including Professor Martin Rossor and nurse Penelope Roques, put out a plea in the Alzheimer’s Society newsletter for people to get in touch if two or more members of their family were affected by Alzheimer’s disease.

The team received copious responses. However, one letter stood out from the rest. It was the 23^rd correspondence in the pile of papers that Professor Hardy had received and it was signed by a woman named Carol Jennings.

In the letter, Carol earnestly detailed how her father, his sister and brother had all developed symptoms and were diagnosed with Alzheimer’s in their 50s, which she illustrated with a hand-drawn family tree.

Reading the words, “please contact me, if you think we should be of help”, Professor Hardy knew that Carol’s case had the potential to help unlock clues as to the cause of the condition – both for those with hereditary Alzheimer’s and in the wider population.

Now a new BBC documentary, The Jennings vs Alzheimer’s, is sharing the story of the Jennings family and how their lives intertwined with researchers at UCL and UCLH to shine a light on Alzheimer’s disease, its causes and even potential cures.

Professor Hardy, who is Chair of Molecular Biology of Neurological Disease at the UCL Queen Square Institute of Neurology, said: “Nobody knew the causes of Alzheimer’s disease, it was just seen as an inevitable consequence of ageing, it was not genetic. So, when we started working on the genetics of Alzheimer’s disease, it was a radical thing to think.”

He added: “When the letters came in, I numbered them and so Carol Jenning’s family in our lab books was always called family 23. I scribbled 23 in the top left hand corner. It was immediately obvious to me that this was an important family.”

After five painstaking years of research, the team discovered a mutation to the amyloid precursor protein (APP) gene, which creates the amyloid plaques that form in the brain during Alzheimer’s disease.

Amyloid initiates a series of pathological processes that involve other proteins becoming toxic - ultimately causing neuronal death and the progressive cognitive and functional decline seen in Alzheimer's that is so devastating.

In those with genetic Alzheimer’s, such as Carol’s family, family members who have inherited the mutation have a much earlier build-up of amyloid in the brain – often decades earlier than is typical. 

The researchers created a test for those at risk to find out if they were going to develop the condition in later years. But, despite having a 50/50 chance of carrying the gene associated with early Alzheimer’s, Carol decided she would rather not know her fate.

She said: “I just don’t see the benefits in knowing, I don’t see what difference it’s going to make. I can live my life quite happily with the doubt that I may get it. You’ve got to die of something, we all have, so why know? Why not just take it when it happens?”

Carol said she’d had a “wonderful” life, with her husband Stuart and their two children John and Emily.

And, after her initial correspondence with Professor Hardy, she continued to visit the UCL Dementia Research Centre and the National Hospital for Neurology and Neurosurgery (NHNN), UCLH, every year, for tests and scans – to allow Alzheimer’s research to progress in the right direction.

The UCL Dementia Research Centre is a hub for patient-centred research into dementia. As well as clinical studies and trials, researchers at the centre focus on identifying and understanding the disease processes that cause dementia and ways to improve diagnosis and treatments.

Carol advocated for the cause for years and even became Vice-President of Alzheimer’s Society. However, at the age of 50 she started to experience the symptoms that she had dreaded all her life and was diagnosed with Alzheimer’s disease at the NHNN by Professor Nick Fox.

From that point, her health began to slowly decline. And sadly, on 29^th March 2024, Carol passed away at the age of 70.

Now, nearly 40 years after Carol’s initial letter, John and Emily must make the same tough decision of whether to find out if they are going to develop early Alzheimer’s and how that might shape their futures.

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Over the past seven years, John has been visiting Dr Cath Mummery and Professor Nick Fox at the UCL Dementia Research Centre and the National Hospital for Neurology and Neurosurgery, UCLH to help support the research that his mother instigated.

John said: “I signed up to begin with to be involved and continue the legacy of the family. Mum had an eye on the future all the time, she wanted science to find a solution to Alzheimer’s disease.”

He added: “It does give my life some purpose thinking that I’m contributing to it.”

In the film, Director of the UCL Dementia Research Centre, Professor Fox, illustrates how the brain changes and loses mass as a consequence of Alzheimer’s disease, by showing John his mother’s brain scans over the years and how they transform following her diagnosis.

He said: “Carol, in a way, is the reason that I’m in research at all. The first gene had been found in 1991 and I started in ‘93. Back then, the brain was a really inaccessible, complex organ. My research was doing brain imaging and MRIs to look at the structure of the brain and detect the earliest changes of Alzheimer’s disease in order to improve diagnosis. It was sad but also a privilege to be part of her clinical care.”

It is estimated that there are currently 944,000 people living with dementia in the UK and 52% of the UK public – 34.5 million – know someone who has been diagnosed with a form of the disease. Over 60% of people living with the condition are thought to have Alzheimer’s disease.

Dementia is the nation’s biggest killer and has been the leading cause of death in women since 2011.

UCL is determined to tackle this growing crisis with one of the world’s largest neuroscience communities, access to a patient population of more than six million and the construction of a new neuroscience facility at 256 Grays Inn Road, enabled by a visionary community of partners and philanthropic funders.

But while the future still remains uncertain for John and Emily, researchers believe we have entered into a new era of hope for Alzheimer’s disease.

In December 2022, “historic” news was heralded as the drug lecanemab was found to slow brain decline in the early stages of Alzheimer’s disease – based on the amyloid cascade theory developed by Professor Hardy in the early 1990s. The drug has now been approved by the FDA in the US and is under consideration in the UK.

Since 2012 Dr Cath Mummery at the UCL Dementia Research Centre has also been leading the UK effort in a global trial of drugs targeting amyloid and other proteins in the brain, aiming to modify the disease and prevent symptom onset in those at risk of genetic Alzheimer’s.

In the initial arm of the trial, patients were injected with an antibody that targets amyloid and removes it from the brain, with the hope of slowing down the disease. The findings from the trial showed that it is possible to modify the biological disease with anti-amyloid treatments.

Carol was the first trial participant.

Dr Mummery said: “It was a huge honour to be able to come full circle and enrol Carol in the first trial to try and prevent Alzheimer’s disease after she had set us on this path.”

And Carol’s impact will continue to resonate through the world of Alzheimer’s research, as her dying wish was for her brain to be donated to scientific research.

Dr Mummery said: “The stakes are really high. There are over 900,000 people in the UK with Alzheimer’s disease right now. If we don’t find a treatment we are going to be in a society that cannot cope with that burden.

“Lecanemab is the first drug that’s got formal approval, which is unbelievable. It’s the first time in Alzheimer’s disease that we have a disease modifying therapy. We are now in the treatment era of Alzheimer’s disease and can build on this to create drugs with greater benefit.

“This is evidence that what we’ve been working on for all these years is finally coming to fruition. It’s the foundation stone that we can build on to make treatments that will have a meaningful impact on people’s lives. That’s extraordinary.”

Professor Fox added: “We are extremely grateful to the staff at The Leonard Wolfson Experimental Neurology Centre and the Queen Square Brain Bank who made filming for this amazing documentary possible – but also very very grateful to Carol and all the families that selflessly contribute to research.

“It is amazing to see how far research has come and I hope we are now on the path to finding a cure for Alzheimer’s once and for all.”

Claire Wood Hill, chief executive of The National Brain Appeal, said: “We were delighted to support the filming of this important documentary about the incredible contribution Carol Jennings made to dementia research. The National Brain Appeal has for many years enabled projects in this field, including the creation of the UCL Dementia Research Centre ​and Rare Dementia Support, a service that provides specialist social, emotional and practical support for people affected by a rare dementia diagnosis, including familial Alzheimer’s disease.”

The Jennings V Alzheimer’s will air on BBC Two at 21:00 on Monday 13^th May 2024.

Links

Find out more about how UCL researchers are spearheading the fight against Alzheimer’s disease.

• Professor John Hardy's academic profile
• Dr Cath Mummery's academic profile
• Professor Nick Fox’s academic profile
• UCL Dementia Research Centre
• UCL Queen Square Institute of Neurology
• UCL Brain Sciences
• UCL Giving: Neuroscience
• National Hospital for Neurology and Neurosurgery, UCLH
• National Brain Appeal
• The Jennings V Alzheimer’s

Images

Top - Bottom

• The Jennings vs Alzheimer's. Credit: BBC
• Carol Jennings. Credit: BBC
• Professor Sir John Hardy, Stuart Jennings, Professor Martin Rossor, Penelope Roques. Credit: Professor Hardy
• The Jennings family. Credit: BBC
• Image of brain scan on a computer. Credit: UCLH
• Dr Cath Mummery and Professor Nick Fox. Credit: UCLH
• The Jennings family. Credit: BBC
• A research scientist working at Queen Sqaure. Credit: UCLH

Video

• The Jennings V Alzheimer's. Credit: BBC

Media contact 

Poppy Tombs

E: p.tombs [at] ucl.ac.uk