Amyloid-beta transmission and Alzheimer’s disease following medical treatments

Dr Gargi Banerjee is a NIHR Clinical Lecturer at the MRC Prion Unit at UCL. Her lectureship, which is also supported by Alzheimer’s Research UK and the Stroke Association, focuses on rare, medically-acquired forms of Alzheimer’s disease and cerebral amyloid angiopathy (CAA), both caused by a build-up of a protein (amyloid-beta) in the blood vessels of the brain.

Between 1959 and 1985, over 1,800 patients in the UK received human cadaveric pituitary-derived growth hormone (c-hGH) for severe short stature and other medical indications. This treatment was halted in 1985 after it was found that some batches were contaminated with prions (infectious proteins), causing Creutzfeldt-Jakob disease, a fatal brain condition. Now, recent research by Dr Gargi Banerjee and colleagues at the MRC Prion Unit at UCL suggests that some people treated with c-hGH may also be at risk of developing Alzheimer’s disease due to amyloid-beta contamination.

Amyloid-beta is a protein fragment that is normally found in the brain. In healthy brains, it is broken down and removed. However, in Alzheimer’s disease, these fragments can clump together to form sticky plaques. These plaques are thought to drive other changes that lead to the symptoms of Alzheimer’s, such as memory loss and cognitive decline. Dr Gargi Banerjee’s recent paper exploring amyloid-beta transmission as a result of historic medical treatments gives us greater insight into the disease mechanisms. Dr Gargi Banerjee explains:

“This research gives us a new framework for how we think about amyloid-beta, and how it causes disease. Diseases caused by transmission of proteins are really rare. People might remember variant Creutzfeldt-Jakob disease (CJD), which emerged as a new disease in the mid-1990s, after material from cows with bovine spongiform encephalopathy (BSE, “mad cow disease”) entered the human food chain.

“CJD is caused by prions – proteins with unusual properties that cause disease by making normal proteins in the brain fold into abnormal shapes. We used to think these properties were unique to prions, but now with this new evidence of amyloid-beta transmission, we are investigating whether amyloid-beta might share some of these unusual characteristics. And if amyloid-beta can and does behave as a prion, this might tell us important things about how and why amyloid-beta causes disease, including in the common ‘sporadic’ (i.e. without an obvious cause) types of Alzheimer’s disease or cerebral amyloid angiopathy (CAA).”

CAA is a condition that much of Dr Gargi Banerjee’s research focuses on. Like Alzheimer’s disease, it is caused by the build-up of amyloid-beta, but instead of forming in the brain tissue itself, in CAA amyloid beta deposits in the walls of blood vessels in the brain, leading to weakened blood vessels and bleeding (haemorrhagic) strokes. It can also cause vascular dementia. “What we don’t know is why some people who have amyloid-beta in their brains develop strokes and vascular dementia (due to CAA), whereas others develop Alzheimer’s disease instead. This is something that my current research is trying to find out.”

Dr Gargi Banerjee and colleagues are currently running experiments that test the idea that CAA and Alzheimer’s disease are different because they are caused by different versions (“strains”) of the amyloid-beta protein.

Dr Gargi Banerjee and colleagues are also looking at the long-term brain health of people at risk of developing medically-acquired CAA or Alzheimer’s disease. “We are setting up a study which invites people at risk to have a comprehensive assessment to look at this. We have set up national and international surveillance studies that centralise information on medically-acquired CAA, and we are using this data to understand more about this condition. We know that people who have medically-acquired forms of CAA and Alzheimer’s disease have been through a unique set of circumstances, and so we are working on setting up a support group for those affected, so that people can share their experiences should they wish to.”

Listening to the experiences of patients and their families is crucial to Dr Banerjee’s work. “For me, practising medicine has always been about these personal and individual stories. These conversations set my research directions and help me to understand what the important questions really are. It’s through listening to someone’s experience of their condition and making shared observations that, as researchers, we learn what we do.”

If you were treated with human cadaveric pituitary-derived growth hormone (c-hGH) in the UK between 1959 and 1985 and would like further information about this research, please contact the National Prion Clinic via email (uclh.prion.help@nhs.net) or by telephone (020 7679 5142 or 020 7679 5036).

Related

Dr Gargi Banerjee's academic profile

MRC Prion Unit at UCL, Institute of Prion Diseases

UCL news: Alzheimer’s disease acquired from historic medical treatments

Banerjee, G., Farmer, S.F., Hyare, H. et al. ‘Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary derived growth hormone’.