Carol Joyce Jennings ( Bexon; born 25 March 1954) is a British campaigner and advocate for research into Alzheimer's Disease. As of 2023 she serves as an honorary Vice-President of the Alzheimer's Society. 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. 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 and provided evidence for the development of the 'amyloid hypothesis', which attempts to explain the underlying causes of Alzheimer's Disease.
Early life and biography
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. It was during this period that her father, Walter, in his mid-50s at the time, began to exhibit symptoms of Alzheimer's Disease.
Discovery of the London Mutation
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. At that time, Hardy was an Assistant Professor of Biochemistry at St. Mary's Hospital, Imperial College London.
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'.
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.
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." The research findings were published in Nature on 21 February 1991., with a summary reported in the British press on 16 February
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.
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.
Later developments and recognition
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.