Action against Alzheimer's

Combatting dementia with state-of-the-art science

In 2016, dementia overtook heart disease as the UK’s biggest killer. An estimated 47 million people worldwide are affected, and every 4 seconds, someone new receives a dementia diagnosis. At present, the most common forms of dementia remain both unpreventable and incurable; but there is hope.

Dementia is a hugely complex condition, but thanks to advanced science and technology, we are gradually unpicking the puzzle.

What is Dementia?

Dementia is not one single disease; it’s a catch-all term for a number of different conditions. Alzheimer’s is the most common form, accounting for about 60% of cases. However, dementia can also result from a number of other conditions.

Whilst there are many different types of dementia, all are related to brain damage. This damage may result from a stroke, trauma or cancer, but by far the most common form of damage is degenerative brain cell death.

However, we’re not sure whether cell death causes dementia, or whether it’s the other way around. In fact, there’s a lot we’re still trying to work out when it comes to dementia. And the biggest mystery of all is what triggers it.

When it comes to irreversible dementias, we’ve yet to identify one clear cause that sets off brain cell death. Many different theories exist, but the search for firm evidence is still on. As part of Alzheimer’s Awareness Month, we’re sharing some of the work taking place on the frontline of science, as researchers strive to unravel the mystery.

Cholesterol’s role

Neuron

(Credit: Renjith Krishnan.r | Dreamstime)

Cholesterol is a fatty substance that exists within our cells. It helps us to carry nerve signals around the body, to digest food and to generate essential substances like hormones and vitamin D.

However, because it’s so important, when things go wrong, cholesterol can cause us problems. High levels can cause a number of fatal diseases, particularly cardiac disorders. Meanwhile, abnormal rates of cholesterol in the brain can cause a build-up of chemicals, which in turn are linked with brain cell death. But much more research is needed before we can fully understand the role that cholesterol may or may not play in Alzheimer’s – that’s why scientists are so eager to find out more.

Neutron scattering experiments at STFC’s ISIS neutron and muon source are helping to reveal more about the behaviour of cholesterol and its associated role in Alzheimer’s disease. These atomic particles can help us track processes that take place at the sub-microscopic level, and so scientists can use neutrons to track the movement of cholesterol through our cells.

By understanding more about the behaviour and movements of cholesterol in the brain, we may be able to learn more about how and why things go wrong. And so, with more research, we should be able to clarify the complex link between unhealthy rates of cholesterol and the types of neurodegeneration we associate with Alzheimer’s disease.

Misfolding proteins

Brain cells

Brain cells exchange electrical signals
(Credit: Rolffimages | Dreamstime)

Proteins are the building blocks of life – we rely on thousands of different types of proteins in our body to create the conditions necessary for life.

All proteins are made up of long chains of amino acids, which are folded up in coil-like shapes. The way that these amino acids are folded is pre-determined and is essential for the protein to do its job. However, sometimes things go wrong, and the amino acids fold up in the wrong way.

When this happens, we know for sure that it can lead to diseases, such as sickle cell anaemia. But scientists think that protein misfolding may also be associated with some forms of dementia, including Alzheimer’s.

The problem is that scientists don’t fully understand the process by which proteins fold. What determines the shape they take? How is the process triggered? These are important questions to answer before we can understand what role protein misfolding might play in dementia.

In recent years, scientists have exploited the SANDALS instrument, located on ISIS STFC’s neutron and muon source, to explore the folding process. Using neutron diffraction, researchers have found that water plays an active role in governing protein folding.

By scrutinising the process on the atomic scale, scientists have discovered that bonding interactions between proteins and hydrogen atoms can trigger proteins to fold in on themselves. This means that water can act as a ‘mediator’ or ‘guide’ for protein folding, making it the primary force driving the process.

If water is as important to this process as it appears to be, it may be that we can one day develop ways of manipulating the interaction so that misfolding events, which are linked to dementia, are prevented.

Toxic iron

Brain

Scanning of a human brain by X-rays
(Credit: Yakobchuk | Dreamstime)

Iron is a naturally occurring substance in the human body – we need it for several vital physical processes. Over the years a lot of evidence has been collected showing subtle differences in trace metals in the brain between people who experience a normal ageing process and people who develop a neurodegenerative disorder like Alzheimer’s disease. Scientists have found increased concentrations of trace iron in the brains of Alzheimer’s patients, particularly in parts of the brain containing ‘lesions’: the abnormal tissue associated with this form of dementia.

However, we’re not sure what the nature of the relationship between the increased iron levels and brain lesions is. Since 2009 scientists have been coming to the UK’s synchrotron science facility, Diamond Light Source, to find out this relationship and to determine other aspects of Alzheimer’s disease.

The researchers used the synchrotron’s bright X-ray beams to study the interactions between the lesions and the iron. Their study revealed that iron was associated with the protein fragment known as ‘beta-amyloid’ found in the brains of Alzheimer’s patients. Close scrutiny of the fragment revealed that it was capable of accumulating iron resulting in increased levels contributing to toxicity. Not only is there an increase of the trace iron, but the beta-amyloid can convert the iron into a potentially toxic form. Eventually, the levels of toxic iron in the brain become too much for us to manage, and brain cells begin to die.

This work suggests that raised levels of iron in the brain as well as the presence of the toxic iron may be caused by Alzheimer’s lesions, leading to increased brain damage. More research is needed before we can fully understand the link, but this work opens up new avenues for the prevention of iron build up, which, in turn, could limit the damage done by Alzheimer’s.

The work could also help to improve diagnostic methods, so that doctors can spot early signs of Alzheimer’s by observing concentrations of toxic iron in the brain.

The Future of Dementia Research

MRI

Magnetic resonance imaging
(Credit: Tomas Hajek | Dreamstime)

Cutting-edge science has always been at the heart of dementia research. For instance, we have the particle physics facility, CERN, to thank for the development of MRI scanners: the machines which help clinicians to diagnose dementia. The technology for these machines originates with superconducting magnet equipment developed by UK physicists for CERN in the 1980’s.

It’s clear that science drives progress in preventing, diagnosis and treating dementia. And so, in order to continue moving forward, it’s vital that we maintain support for the research facilities that underpin this important work.

To this end, the UK government recently invested £100 million in a new research institute for medical sciences, which will focus on combatting on challenging diseases such as dementia. Located on the Harwell Campus in Oxfordshire, the new Rosalind Franklin Institute (RFI) will bring together UK expertise to develop new technologies that will transform our understanding of disease and speed up the development of new treatments.

The RFI will bring together academic and industry researchers from across the UK to develop disruptive new technologies designed to tackle major healthcare challenges and accelerate the discovery of new treatments. As such, dementia research in the UK is likely to benefit tremendously from the introduction of the RFI in future.

Defeating Dementia

State-of-the-art science and technology can help us piece together the puzzle underlying dementia. There’s still a great deal we don’t understand when it comes this highly complex condition, but we are moving gradually closer towards answers.

Dementia remains a life-changing diagnosis, but that doesn’t mean that we’re powerless to stop it. Every day, scientists are driving research forwards, and in time their work may create a better future. Thanks to cutting-edge research, we have a better understanding of dementia; we have a growing foundation of knowledge from which to build from; and, most importantly of all, we have hope.

Science and Technology Facilities Council Switchboard: 01793 442000