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Carol Jennings
Born
Carol Joyce Bexon

(1954-03-25)25 March 1954
Nottingham, England
Died29 March 2024(2024-03-29) (aged 70)
Coventry, England
NationalityBritish
Years active1986–2024
Known forAlzheimer's disease activism

Carol Joyce Jennings (née Bexon; 25 March 1954 – 29 March 2024) was a British campaigner and advocate for research into Alzheimer's disease. She served as an honorary Vice-President of the Alzheimer's Society until her death in 2024.[1] Through her activism in the 1980s, Jennings brought her family to the attention of researchers studying the disease, which subsequently led to the discovery of the London Mutation.[2][3] This mutation, found on the Amyloid Precursor Protein (APP) gene located on chromosome 21, marked a significant breakthrough in understanding the genetic basis of Alzheimer's disease[1] and provided evidence for the development of the 'amyloid hypothesis', which attempts to explain the underlying causes of Alzheimer's disease.[1][4]

Early life and biography

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Jennings was born in Nottingham, England, to Joyce and Walter Bexon. She received her education at Bilborough Grammar School and later attended Chester College, where she completed her teacher training. She went on to marry Stuart Jennings, a Methodist minister and historian, and they had two children.[5][6] It was during this period that her father, Walter, in his mid-50s at the time, began to exhibit symptoms of Alzheimer's disease.[7]

Discovery of the London Mutation

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By the mid-1980s, three of Walter's siblings also displayed signs of Alzheimer's disease, with symptoms emerging much earlier than expected—in their 40s and 50s. Convinced that there must be a genetic link and determined to find answers, Jennings wrote a letter to the research team led by John Hardy in the spring of 1986.[8] At that time, Hardy was an Assistant Professor of Biochemistry at St. Mary's Hospital, Imperial College London.[3]

Genetic Alzheimer’s is rare, accounting for only about 1% of Alzheimer’s cases, but Hardy believed that Jennings’s family could provide clues to the cause of the condition in the wider population, known as 'sporadic Alzheimer's disease'.[4]

To explore this possibility, Professor Hardy and his team of scientists and clinicians, including Professor Martin Rossor collected blood samples from the Jennings family to compare the genetic differences between those who developed Alzheimer's and those who did not. The search took about five years. From the blood samples, DNA was extracted, and Hardy’s team used the Southern blotting technique to examine the genes on chromosome 21. This chromosome was chosen because individuals with three copies of chromosome 21 (Down syndrome) all develop Alzheimer's disease.[9]

The breakthrough came in 1991. Alison Goate, a junior researcher on the team, uncovered the specific gene mutation responsible for the disease in Jennings’s family. Goate, now a professor at Icahn School of Medicine at Mount Sinai, NY, later recalled the discovery as a "eureka moment."[8] The research findings were published in Nature on 21 February 1991,[10] with a summary reported in the British press on 16 February.[11][12][13]

The mutation, known as the 'London mutation,' affects the amyloid precursor protein (APP) gene, leading to the formation of amyloid plaques in the brain. Amyloid disrupts normal brain processes by overactivating brain cells and causing ongoing inflammation. It can also impact blood flow and have an impact on other proteins in the brain. When excessive amyloid accumulates, it can interact with the toxic protein tau, causing neuronal death and the symptoms of Alzheimer's disease. In those with genetic Alzheimer’s, this process occurs early because the patient produces too much APP. However, the same process also happens in those with non-genetic Alzheimer’s, albeit at a slower rate.[9]

In 1992, as a direct result of the discovery of mutations in the APP gene, Professor Hardy and Professor David Allsop published the amyloid cascade hypothesis. They hoped that this hypothesis would help in designing drugs to intervene in the disease's progression, influencing the direction of Alzheimer’s research for the following three decades.[4]

Later developments and recognition

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After the discovery of the London mutation, Jennings left her teaching career to work in Alzheimer’s advocacy full-time. Initially, she served as the Alzheimer's Society’s first Coordinator for Younger People with Dementia and later worked with smaller dementia charities while also functioning as an independent advocate for dementia caregivers.[14]

As the amyloid cascade hypothesis gained momentum, Professor Hardy received recognition for his contributions to the field. In 2015, Hardy became the UK’s first recipient of the Breakthrough Prize in Life Sciences for "discovering mutations in the amyloid precursor protein (APP) gene that cause early-onset Alzheimer’s disease, linking the accumulation of APP-derived beta-amyloid peptide to Alzheimer’s pathogenesis, and inspiring new strategies for disease prevention." In his acceptance speech for this award, he expressed special gratitude to Jennings’s family. In 2018, Hardy, alongside Christian Haass, Bart De Strooper and Michel Goedert, was honoured with the Brain Prize for "ground-breaking research on the genetic and molecular basis of Alzheimer’s disease."[15]

Over time, researchers have expanded upon and challenged this hypothesis, but developing drugs that target amyloid proteins has proven to be a significant challenge, with many failures, underwhelming results, and dangerous side effects reported.[16]

When Jennings herself began to develop symptoms of Alzheimer's disease in 2008, she took a step back from her speaking and advocacy work.[17] However, with the development of new and successful anti-amyloid treatments, journalists and researchers rekindled their interest in the origins of the amyloid hypothesis and Carol Jennings's involvement.

One such success was shown in a large-scale trial of the monoclonal antibody treatment lecanemab. Professor Hardy described the outcome as both "modest" and "historic," and hailed it as the beginning of the end for Alzheimer's disease. In particular, there is hope that anti-amyloid therapies could eventually be used to prevent the disease ever progressing to the symptomatic stage.[18] This resulted in renewed press interest in the Jennings family, and their contribution was once again covered by the press.[19]

In 2023, both Carol and Stuart Jennings were appointed honorary Vice-Presidents of the Alzheimer's Society, acknowledging their "extraordinary contribution to the field of dementia research".[1][20] To further honour their legacy, a new research fellowship was launched to support emerging researchers in Alzheimer’s disease. In February 2024, Dr. Jo Jackson was named the first recipient of the Carol Jennings Fellowship.[21] Dr. Jackson’s research utilises advanced techniques to investigate the role of genetics, proteins, and other factors in making synapses vulnerable to damage in Alzheimer’s disease.[22]

Jennings died on 29 March 2024, four days after her 70th birthday.[23][24][25]

The Jennings vs Alzheimer's

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In 2022, the BBC announced the commissioning of a feature documentary recounting the story of the Jennings family and their ongoing involvement in Alzheimer's research.[26][27] The resulting film “The Jennings vs Alzheimer’s” was broadcast on BBC Two and BBC iPlayer on 13 May 2024 in the UK.[28] Directed by Irish filmmaker Niamh Kennedy, the documentary received positive reviews from major newspapers, including The Guardian,[29] The Times,[30] and The Daily Telegraph.[31] It won the award for the Best Science Documentary category at the 2024 Grierson Awards.[32][33]

See also

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References

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Citations

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  1. ^ a b c d "Honouring a couple affected by dementia for their contributions to dementia research". Alzheimer's Society. Retrieved 12 September 2023.
  2. ^ "APP V717I (London)". Alzheimer Research Forum. Retrieved 12 September 2023.
  3. ^ a b HIH.gov Archived 5 November 2011 at the Wayback Machine
  4. ^ a b c "Feature: The 'historic' Alzheimer's breakthrough that is 30 years in the making". University College London. 2 December 2022. Retrieved 12 September 2023.
  5. ^ Zhang, Gary (30 July 2017). "Three generations of a British family are helping the fight against Alzheimer's". i. Retrieved 13 September 2023.
  6. ^ Scougall, Murray (5 December 2016). "Rare hereditary form of dementia casts shadow over family". The Sunday Post. Retrieved 13 September 2023.
  7. ^ "Carol's story: dementia in the family". FutureLearn. 25 March 2016. Retrieved 12 September 2023.
  8. ^ a b "A Eureka Moment: Carol's Story". University College London. 19 September 2018. Retrieved 12 September 2023.
  9. ^ a b Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André (September 2015). "A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome". Nature Reviews Neuroscience. 16 (9): 564–574. doi:10.1038/nrn3983. PMC 4678594. PMID 26243569.
  10. ^ Goate, Alison; Chartier-Harlin, Marie-Christine; Mullan, Mike; Brown, Jeremy; Fidani, Liana; Giuffra, Luis; Haynes, Andrew; Irving, Nick; James, Louise; Mant, Rebecca; Newton, Phillippa; Rooke, Karen; Roques, Penelope; Talbot, Chris; Pericak-Vance, Margaret; Roses, Alien; Williamson, Robert; Rossor, Martin; Owen, Mike; Hardy, John (21 February 1991). "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311): 704–706. Bibcode:1991Natur.349..704G. doi:10.1038/349704a0. PMID 1671712. S2CID 4336069. Retrieved 12 September 2023.
  11. ^ Mihill, Chris (16 February 1991). "Defective gene link to dementia disease". The Guardian.
  12. ^ Highfield, Roger (16 February 1991). "British first to find a cause of Alzheimer's". The Daily Telegraph.
  13. ^ Prentice, Thomson (16 February 1991). "Family link leads to breakthrough on Alzheimer's Disease". The Times.
  14. ^ "Services for younger people with Alzheimer's disease and other dementias" (PDF). Royal College of Psychiatrists. Retrieved 13 September 2023.
  15. ^ "Alzheimer's Disease - The Lundbeck Foundation". Lundbeck Fonden. Retrieved 12 September 2023.
  16. ^ Vogt, Anne-Cathrine S.; Jennings, Gary T.; Mohsen, Mona O.; Vogel, Monique; Bachmann, Martin F. (15 February 2023). "Alzheimer's Disease: A Brief History of Immunotherapies Targeting Amyloid β". International Journal of Molecular Sciences. 24 (4): 3895. doi:10.3390/ijms24043895. PMC 9961492. PMID 36835301.
  17. ^ Yedroudj, Latifa (8 April 2023). "The Coventry woman who became a pioneer in Alzheimer's research". Coventry Telegraph. Retrieved 13 September 2023.
  18. ^ Abbott, Alison (16 June 2022). "Treating Alzheimer's Before It Takes Hold". Scientific American. Retrieved 13 September 2023.
  19. ^ Whipple, Tom (18 June 2021). "Has this man found the key to the Alzheimer's time bomb?". The Times. Retrieved 13 September 2023.
  20. ^ "Carol and Stuart Jennings – Vice Presidents at Alzheimer's Society". Alzheimer's Society. 30 March 2023. Retrieved 12 September 2023.
  21. ^ Jackson, Jo [@jojacksonhere] (22 February 2024). "Thrilled to be named as an @alzheimerssoc Dementia Leader, the 1st recipient of the Carol Jennings Fellowship and supported by the Hamilton Neal fund" (Tweet). Retrieved 24 July 2024 – via Twitter.
  22. ^ "From academia to industry and back again: in conversation with Dr Jo Jackson". UK Dementia Research Institute. 21 February 2024. Retrieved 24 July 2024.
  23. ^ "It's with great sorrow that we share the... - Alzheimer's Society". Facebook. Retrieved 11 April 2024.
  24. ^ "Circuit News, April 2024". Woodside Avenue Methodist Church Centre. Retrieved 21 April 2024.
  25. ^ "Carol Jennings, whose family's genetics informed amyloid cascade hypothesis, dies at 70". The Transmitter: Neuroscience News and Perspectives. 30 April 2024. Retrieved 5 May 2024.
  26. ^ "BBC announces new documentaries at Sheffield Doc/ Fest 2022". BBC. Retrieved 12 September 2023.
  27. ^ "Family 23: BBC Two Announce new intimate family documentary". TV Zone UK. 30 June 2022. Retrieved 12 September 2023.
  28. ^ "The Jennings vs Alzheimer's". BBC. Retrieved 24 July 2024.
  29. ^ Mangan, Lucy (13 May 2024). "The Jennings v Alzheimer's review – how one letter caused a medical revolution". The Guardian. Retrieved 24 July 2024.
  30. ^ Dowell, Ben (13 May 2024). "The Jennings vs Alzheimer's review — would you want to know if you had the gene?". The Times. Retrieved 24 July 2024.
  31. ^ Rees, Jasper (13 May 2024). "The Jennings v Alzheimer's: a fascinating insight into one woman's selfless sacrifice". The Telegraph. Retrieved 24 July 2024.
  32. ^ "BBC tops Grierson awards shortlist". Televisual. 22 July 2024. Retrieved 24 July 2024.
  33. ^ @griersontrust (6 November 2024). "The #GriersonAwards winner for Best Science Documentary goes to The Jennings vs Alzheimer's 🌟 - presented by @lizbonnin" (Tweet). Retrieved 6 November 2024 – via Twitter.

Works cited

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  • Armstrong, Sue (2019). Borrowed time: The Science of How and Why We Age. London: Bloomsbury Sigma. ISBN 978-1-4729-3606-6.
  • Jebelli, Joseph (2017). In Pursuit of Memory: The Fight Against Alzheimer's. London: John Murray. ISBN 978-1-473-63576-0.
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