 So Alzheimer's disease is a progressive disease, so we know that it starts and initiates a change in the neurochemistry and the chemicals within our brain that ultimately leads to the death of nerve cells. So what causes brain cell death in Alzheimer's disease is one of the questions that's still unresolved. We know a lot about all the different elements which contribute to the cell death but pinpointing it to one factor has eluded us as yet and that's why it's such a challenge in making a drug or a medicine to prevent that nerve cell death. Two toxic peptides have a role to play. There's the amyloid beta peptide and also the tau peptide. And these are seen as toxic entities which actually accumulate within the brain and actually almost suffocate the brain cells and then lead to that neuronal cell death. Indeed we know that for those under the age of 65 that develop Alzheimer's disease known as early onset, there's a genetic component. So in the case of early onset and the genetic factors that play a role, we know that they centre around the processing of that amyloid beta peptide that's toxic to the nerve cells. And that's opened up our avenues to explore anti-amyloid therapies to try and prevent that accumulation. So anti-amyloid drugs and medicines are in clinical trials and we recently had the approval of the first Alzheimer's medicine at the start of July which is targeting that amyloid beta peptide and looking to break down those plaques and accumulations that develop in those living with dementia. Another route which may provide a more long term solution is to think about the inflammation that occurs in the brain. And as scientists we believe that occurs some 20 years before people go into the doctor with changes in their memory or behaviour. But some of these subtle changes in the chemistry in our brain are very hard to detect and that's what as scientists and clinicians we're struggling with is to get better diagnostic tools that can pick up those early changes and allow us to intervene more quickly. So cell culture for us is a fundamental part of the research that we do. And here we use animal cells such as mice and rats and culture nerve cells in a dish. Alongside those we use human cells so stem cells that have been converted into neurons. In culture we can start to expose those cells to some of those toxic entities that we know are involved in the human disease such as the amyloid beta peptide or the taupeptide. And we can look to see what changes occur in the activity of those cells and if we can prevent those changes through drugs or medicines. So one cell type we're particularly interested here at the University of Reading is microglia or the brain macrophage. So they're in essence the guardians of the brain and indeed we believe that they are first responders. So in the healthy brain the microglial cells that we're interested in are involved in clearing away debris and also starting to attack pathogens that enter the brain. So they're protecting those nerve cells and keeping them free from disease. But as the disease takes hold and we see changes in those neurons and they start to become dysfunctional, the microglial get the signal to then come and actually start contributing to the disease process itself. They in essence start to engulf some of those synapses, those connections between nerve cells and that leads to a loss of signalling within the brain. So we've gone from in a healthy brain a good cell that protects the nerve cells to something that very much contributes to the disease state. So we can take cultures of these microglial cells, expose them to the amyloid beta peptide and monitor the chemicals that they are secreting. So it almost gives us a fingerprint or in essence a snapshot of what that cell is doing when it's being exposed to the amyloid beta peptide. We can then put that back into the bigger picture. What that microglial cell is secreting, is it protective to the nerve cells or is it actually going to be actually harmful to the nerve cells? And we can then start to dissect some of the pathways involved to generate new molecules for drugs and then go on to develop new medicines. So as part of our research we're using genetically modified mice to mimic the human disease that we're interested in which is Alzheimer's disease. So once we've sacrificed the animal we quickly remove the brain and then we then look to section the brain into individual slices which allow us to identify different brain regions. We can then transfer the brain slices to our electrophysiological rig set up behind me to start to investigate some of the electrical properties of those slices. So we can then implant the electrode into the slice and start to record from individual nerve cells to look how that electricity that they generate is changed as part of the disease process. So we do know that some of the early changes in Alzheimer's disease in humans and as well as in animal models are changes in that electrical activity. We see an increase or a hyper excitable state within the nerve cells of the brains of individuals living with dementia but also in some of the animal models we use to actually better understand the disease. So using mice in dementia research may seem very abstract but indeed it's a useful tool and one that researchers have used for decades. So in studying it in mice we have to genetically modify the animals. So mice naturally do not get Alzheimer's disease. So we have to change their genetic makeup in order that they start to produce or overproduce some of the proteins that we've mentioned the amybeta and the tau protein. So by changing the genetic makeup we can accelerate the deposition or the accumulation of the amybeta peptide within the brains of these mice and we can actually map on the progression of the disease as the mice age. And we see that some of those actual characteristics and symptoms that the mice show map nicely on to the human disease. So for example we know that the electrical activity in the human brain changes as the disease progresses and that's something we can monitor in our mice or mouse models. So the genetically modified mice while we are changing their brain and we see some memory deficits as they age to look at them you would not notice any difference to those of their wild type litter mates. So there's no obvious stress to these animals. They live approximately 18 months and that's when in essence researchers would then look to investigate their brains and do some of the research and experiments we've talked about earlier today. So currently the medicines and drugs that are used to manage dementia rely on a diagnosis and that occurs when some of that brain cell death has already occurred. What the research has shown us is that those subtle changes in the chemistry occur some 20 years before that positive diagnosis. So what the research now is starting to investigate and trying to pick up is something that's actually occurring within the blood or indeed the fluid that surrounds the brain. So the search is on for a biomarker, some biological sample or fluid that can actually detect those early changes. By understanding that biomarker we can use that hopefully to improve diagnostic tools and then that can lead on to actually opening up avenues to developing treatments for those that have shown that positive biomarker. So while the dementia landscape in terms of medication hasn't changed as rapidly as we would like to, there's really been some positive changes in our understanding of the disease. And that happens through the use of animal models and complementing that with some of the new stem cell technologies that are available to scientists. Our studies are looking to explore much more in depth around the inflammation and some of the different cell types in the brain. We're interested in microglia or brain macrophages and the role that they play in contributing to the disease. Our hope is that we can one day find a switch within those cells that will allow us to prevent that nerve cell death that is evident in the disease. To date we're slowly starting to unpick some of the protein players that change the function of these cells. The next step in our journey is trying to find molecules that can modify the activity of those particular proteins. That will then start the journey of drug discovery to hopefully enter clinical trials and offer hope to those living with dementia.