The University of Southampton
Research

The challenges of ageing

Vaccinations could prevent against Alzheimer’s disease

Published: 2 November 2016

By 2050, the number of people in the UK aged over 80 years is projected to reach eight million, with one in four of us being 65 or over. This increasing longevity is in some respects cause for celebration, but it also brings significant challenges in terms of health and social care.

One of the greatest challenges is the rising number of people with dementia. There are over 100 different types of brain disorders and illness which can cause dementia, the most common being Alzheimer’s disease. One in three people will live to develop some form of dementia, which currently costs the UK £539 per second.

Dementia causes a loss of memory and brain function that is usually progressive and eventually severe. Given that the brain has a limited ability to repair itself, intervention before damage can occur is the ideal approach. Researchers at Southampton have discovered that this might be a possibility, through vaccination that would kick-start the immune system.

Alzheimer’s patients develop an abnormal build-up of two different proteins in the brain – amyloid beta that forms plaque that stops the brain from signaling and Tau protein, which builds up inside the nerve cells. 

“Through vaccination, could you prompt the body’s immune system to stop the build-up of protein and reduce damage to the brain? That‘s the story that has been unfolding for 15 years,” says James Nicoll, Professor of Neuropathology at Southampton. An experimental study in mice showed that it was possible to stop the build-up of plaques and even provoke some removal. A subsequent human clinical trial, conducted at Southampton’s Memory Assessment and Research Centre, became the first ever trial in the world for a vaccine for Alzheimer’s disease.

Since the trial, James together with Clive Holmes, Professor of Biological Psychiatry, and Delphine Boche, Associate Professor in Clinical Neurociences, has carried out a further study that showed that amyloid immunisation alters Alzheimer’s by removing plaques from the brain. “That was possibly the first treatment for Alzheimer’s that can change what is going on in the brain,” explains James. This finding was identified by 34 leaders in the field as one of the most notable advances in Alzheimer ’s disease (Nature Medicine, 2006).

However, our unique angle is that we have brain tissue donated from patients that have been vaccinated, and can do studies in a way no-one else can. We have identified that the side effects are likely to be related to the blood vessels in the brain. We have found that while the plaques can be cleared from the brain, they then seem to build up in the walls of the blood vessels, with an increase in amyloid protein in the cerebral vasculature leading to serious side effects including an increase in cortical microhaemorrhages (micro bleeds in the brain).

James Nicoll - Professor of Neuropathology at Southampton

Southampton’s unique role

“Trials of the original vaccine were stopped because of unanticipated side effects, which has meant that despite great efforts and expense, disappointingly, the field has been stuttering for quite a few years,” continues James.

“However, our unique angle is that we have brain tissue donated from patients that have been vaccinated, and can do studies in a way no-one else can. We have identified that the side effects are likely to be related to the blood vessels in the brain. We have found that while the plaques can be cleared from the brain, they then seem to build up in the walls of the blood vessels, with an increase in amyloid protein in the cerebral vasculature leading to serious side effects including an increase in cortical microhaemorrhages (micro bleeds in the brain).”

James is also investigating the brain’s vascular system, the distribution of blood flow within the brain, and why treatments to prevent vascular diseases seem to be helping with rates of dementia.

“It seems that treatments for diabetes, reduction of blood pressure, and lipids are also contributing to a reduction in the rate of dementia. It implies that blood vessels in the brain play an important role in cognitive function,” says James.

A third main area concerns the role of inflammation in the brain in Alzheimer’s, a line of interest that has been boosted by recent genetic studies, allowing for a view of the entire genome and the identification of genetic risk factors for disease which has highlighted genes in inflammatory processes as being important in Alzheimer’s.

One challenge facing researchers is the length of time taken before results can be seen. “Despite more than 40 clinical trials over 16 years involving many thousands of patients, we know that the vaccine approach alters what goes on in the brain, but not yet whether it will be a useful treatment. It seems it might not be useful in Alzheimer’s once the problem is established, but a more interesting idea for very early stages or prevention of the disease. But because the progression of dementia happens relatively slowly over a number of years, it inevitably takes many years to conduct the studies.”

Ageing through a citizenship lens

Given that no cure is yet imminent, the more immediate challenge becomes supporting the growing number of older people with dementia. That means looking beyond pure care needs, believes Dr Ruth Bartlett, Associate Professor in Health Sciences at Southampton, whose research focuses on bringing a citizenship lens to the field of ageing and dementia. “We need to consider the whole life situation that someone with dementia is experiencing. That means broadening the lens to not only think about a person’s care needs but also their rights, their connections with their community and neighbourhood, and the contribution that they might wish to make to society,” she says.

Ruth is Principal Investigator on a project funded by the Alzheimer’s Society researching the use and effectiveness of GPS technologies in relation to people with dementia. Following the issue of GPS technology by a Sussex police force to families of people with dementia, concerns were raised as to the ethics of such a move. “I was interested to hear the perspective of the individuals and families who were using the technology. If there was technology available that helped people with dementia stay safe, and connected with their communities, I wanted to explore its usefulness and effectiveness.” The aim of this 28-month study, is to produce practical guidance in collaboration with nurses and other health professionals, families and other stakeholders to help make better decisions as to GPS technology usage. Dr Tula Brannelly is a Senior Research Fellow working full time on this project.

Ruth is also co-Director of Southampton’s Doctoral Training Centre sponsored by a £430k Alzheimer’s Society funding grant for students to research aspects of enabling risks through a care and citizenship lens. “There can be a tendency to wrap people in cotton wool once they have dementia. A citizenship approach is about weighing up the pros and cons as to what risks it would be safe for people to take,” explains Ruth. Research areas include mobility within a hospital environment and risk taking in care homes. The supervisory team, including Ruth, is based across Health Sciences and Gerontology and has close connections with NIHR CLAHRC Wessex, which has adopted ageing and dementia as one of six research themes.

Because of the growing complexity in this area, collaboration and strengthening capacity is becoming increasingly important. “We have a growing cohort of students and academic staff doing research around improving care and quality of life for older people, in particular people with dementia. Everyone is part of the Health Sciences’ newly established research group on ageing and dementia led by Professor Jackie Bridges. ”

The University also offers an MSc in Complex Care in Older People. “There is recognition that there is a growing ageing population, many of whom will have complex care needs related to dementia and other health conditions. The MSc programme is for those people working with older people who need specialist skills and knowledge to respond appropriately to those complexities.” As the challenges of ageing become increasingly complex, the greater the need for better education and research.

More information on James's research

More information on Ruth's research

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