UCL Division of Biosciences


Professor Frances Edwards

And here Professor Frances Edwards, explains that she will be talking about her new Alzheimer’s dis-ease hypothesis: Connecting the dots in Alzheimer’s disease; it takes two to tangle.

“Finding treatments that prevent or slow the progression of Alzheimer’s disease is the most urgent medical challenge of our time. As treatments for other conditions, such as cancer and heart disease, improve we are living longer and the numbers of people with Alzheimer’s disease is escalating. Not only does this have massive personal cost, it is also a major financial burden both privately and publicly with the present cost of Alzheimer’s disease in the UK estimated at more than £26 billion each year.

The events that occur which lead to Alzheimer’s disease can be well described. Initially there is an increase in a substance called amyloid beta that is released from neurones, the nerve cells of the brain, and which becomes toxic to neurones if there is too much of it around. We don’t know much about why it is released or whether this happens in all people or only in those who later show symptoms of the disease. If the amyloid beta cannot be sufficiently cleared away, it builds up and starts to be deposited. This makes solid lumps called plaques that gradually grow between the brain cells. In and around the plaques there is damage to synapses, the tiny connections by which neurones communicate.

This process continues in the brain for decades without us having any idea that it is happening. Then at some stage another problem starts to build up. Tau is an important protein inside cells that binds to microtubules in the axon, the long thin tube that carries messages away from a neurone, sending communication out to the synapses. This connectivity between neurones around the brain makes up an incredibly complex neuronal network that underpins all our thought processes and our ability to lay down and recall memories.  If Tau changes its form it can fall out of the axon and get tangled in other parts of the cell, upsetting communication between the neurones and eventually causing their death. This can happen to a certain extent at any time and all brains probably contain some Tau tangles, but, in Alzheimer’s disease, as the plaque load increases the Tau tangles start to build up until they cause the network of communication to start to fail. It is only at this stage when many neurones have died that the disease is finally diagnosed.

At this stage the brain is failing, memory is deteriorating and so are many other processes such as speech and the general organisation of logical thought processes. There are some drugs that help a bit with these symptoms but nothing that prevents the ongoing process of decline.

Although we can describe this series of events, we know very little about the causal links that result in this devastating progression. In the research in the Edwards lab we are interested in trying to understand what connects these events and why one stage leads to the next. We know quite a lot about which genes can contribute to the progression of the disease. Recently a new player has also been added to this story. From comparing the genetics of people who have Alzheimer’s disease to those that don’t, it has become clear that genes that are important in microglia, the immune system of the brain, are extremely important. People with microglial genes that function poorly have a higher risk of being diagnosed with Alzheimer’s disease.

Scientists around the world are working on all the parts of this disease progression. We are trying to understand why amyloid beta builds up, why it is toxic but doesn’t cause dementia until Tau is involved, how plaques are linked to development of Tau tangles, why Tau falls out of the axons, why there is such a delay between the initial build-up of plaques and the final degeneration of the neuronal network. Why can some people have a heavy load of amyloid plaques but not have any sign of dementia? What is the role of the immune system at different stages of the disease?

Each of these points is complicated and difficult and as scientists, we tend to focus down on a small section and beaver away trying to understand our own little part of the disease. This produces many small somewhat disconnected pictures of different aspects of the disease. In contrast the medical profession tends to look at the person as a whole, not separating the microscopic parts but also unable to understand the underlying cause of disease progression.

Recently I have tried to look across all the different stories to try ‘to connect the dots’ of scientific progress. To find a prevention or cure for this devastating condition, we need to work out how the different parts we study in science build up to the whole disease picture that finds its way to the clinic.”