A new era for dementia research
There are 55 million people living with dementia worldwide, with numbers expected to almost triple to 153 million by 2050. Dementia is currently the leading cause of death in England, yet despite the tremendous social and financial implications of these figures, there is no cure for dementia.
Although dementia and Alzheimer’s disease (AD) are quite often used interchangeably, they are very different things. Dementia is not a disease, it is a symptom, or rather a group of symptoms, that affect the brain in devastating ways that interfere with everyday life. These include memory loss, confusion, difficulty concentrating or problem solving, as well as issues with spatial awareness.
Although dementia develops with age, it is not part of normal ageing. The underlying causes of dementia are varied and although it mostly arises from neurodegenerative disorders, there are other conditions that may lead to dementia or dementia-like symptoms including infection or acute injury.
microglia (green) and amyloid plaques (misfolded protein clusters, red) from post-mortem tissue of an AD patient. Credit: Millie Thackray
AD is the most common cause for dementia, contributing to 60-70% of dementia cases. It is characterised by the accumulation of misfolded proteins into abnormal clusters in the brain.
The biggest challenge in AD research is not only that it affects the most complex and least understood organ in the body, but that people don’t normally exhibit the symptoms of AD until they reach their 60s. We now know that there are biochemical and cellular changes already happening in the brain two or three decades prior.
So how do we treat a disease that we don’t even know is there until it’s too late? Key to this will be identifying biomarkers for the early diagnosis of the disease, as well as trying to understand the biochemical and cellular changes that happen in the brain at the early stages of the disease.
Our work at the Crick
In our lab we are using exciting new technology to directly investigate the cellular changes that happen in the brain during the development of AD. We have a special interest in microglia, the immune cells of the brain, as they have recently been identified as key players in the development of AD. It is clear though that AD progression is a complex multicellular process, so we are keen to address how microglia responses affect other brain cells such as astrocytes and neurons.
We are extremely privileged to be part of three different institutions: UK Dementia Research Institute (UK DRI), UCL and the Crick. As such we can benefit from a multi-disciplinary environment and share access to great technology.
Most importantly we have amazing colleagues, all of them world leaders in their field. This means that we have been able to establish incredible collaborations and have regular discussions that draw from experiences in different fields to help us better understand the biology of this disease. For example, we’ve teamed up with the Sex Chromosome Biology Lab here at the Crick to investigate possible causes for why females have a higher incidence of AD than males.
The importance of funding
The UK Government has recently pledged to double their funding for dementia research to £165 million a year. This may seem like a large sum, but it is overshadowed by the total cost of dementia of care for people with dementia in the UK, which is £35 billion a year. Two thirds of this is being paid by the patients and their families.
As the number of people living with dementia is increasing, this figure will continue to rise, highlighting an immense crisis for which an urgent solution is needed. The Government’s investment into dementia research is absolutely needed and will give scientists the means to broaden our understanding of the disease, identify more biomarkers and generate more drug trials.
Three decades ago cancer was the leading cause of death in the UK. Thanks to major investments from governments, the public (through charitable donations) and a strong global joint effort to tackle the disease, we have seen incredible progress in understanding the biology of the disease, diagnostics, prevention and therapies.
There is still a long way to go with cancer research, but cancer survival in the UK has doubled in the last 40 years. The number of findings on cancer research is continuously growing, and in PubMed there are over 4.5M papers focused on cancer.
In contrast, there are currently over ten times fewer publications dedicated to dementia compared to cancer and this is mirrored by a comparable difference in funding over the years. The time has come now, for a similarly joint effort in tackling the current most urgent medical crisis we are facing.
The future of dementia research
The devastating effect of the coronavirus pandemic on dementia patients and their families has been well documented. In addition, the pandemic has had a massive impact on Alzheimer’s research. In the lab this has been most evident, not just in the time that was lost during the lockdowns, but the knock-on effects which still last today, such as issues accessing consumables and training.
In addition, we have seen a significant loss of funding as charities experienced difficulties to raise money. But the pandemic also highlighted how, when faced with a crisis, scientists can work together to find treatments and therapies for a disease. We are now at a turning point for dementia research. Over the last decade we have made huge advances in better understanding the genetic risk to developing neurodegenerative diseases, there have been major strides in technology and a revolution in data science.
The acceptance of the complexity of the diseases that cause dementia have led to an increase in collaborations (like the creation of the UK DRI and Dementias Platform UK, among others) and a realisation of the need for multidisciplinary approaches. All the key ingredients for success are here now, and we need to continue to increase awareness, raise funding and recruit brilliant minds to work together and find new therapies for the prevention of dementia.
