MRC researchers win prestigious awards for contribution to neurodegeneration research
17 Aug 2017
This case study forms part of our Investing for Impact report, looking at how MRC- funded research delivers impact. More can be found in the Investing for Impact section of our website.
Two MRC-funded scientists were recognised for their invaluable contributions to neurodegeneration research with the prestigious Brain Prize award in 2018. By identifying key genetic mutations contributing to neurodegeneration, these researchers transformed our understanding of the mechanisms of neurodegeneration.
Professor John Hardy at University College London and Professor Michel Goedert at the MRC Laboratory of Molecular Biology have been studying neurodegeneration for decades. Their understanding of the activity of the mutant genes beta amyloid and tau has been instrumental in helping scientists understand the mechanisms underpinning disease. Professor Hardy’s and Goedert’s research contributions were recognised in 2018 when they were awarded the prestigious Brain Prize, with €1 million prize money, alongside Professor Bart De Strooper (Director of the new UK Dementia Research Institute at UCL) and Professor Christian Haass (Ludwig-Maximilians-Universität München, Germany). Professor Hardy’s research contributions were previously recognised in 2015 when he was the first UK scientist to be awarded the prestigious Breakthrough Prize in Life Sciences, with $3 million prize money. Likewise, Professor Goedert won the 2014 European Grand Prix for Research for his contributions to the field, and both these researchers have been elected as Fellow of the Royal Society.
A key focus of current neurodegeneration research is on disease mechanisms. Learning more about these mechanisms will help us to develop more effective treatments and, potentially, find ways of preventing dementia from developing in the first place.
Ever since German psychiatrist Alois Alzheimer identified the first case of what became known as Alzheimer's disease in 1901, our understanding of this disease has grown. Early research focused on studying brain samples from autopsies of patients who had Alzheimer’s disease. These studies showed many otherwise healthy nerve cells had small, round clumps, or “plaques” between them, along with unusually thick and impenetrable fibres or “tangles” along the neuronal extensions. These plaques and tangles became the twin hallmarks of Alzheimer’s disease showing the difference between a healthy brain and a diseased one that had undergone neurodegeneration. This also provided one of the first physical links between dementia and neurodegeneration.
But what are these plaques and tangles? How do they form, and more importantly, could stopping them prevent the progression of neurodegeneration? Researchers studying these questions identified that a protein known as amyloid beta misfolds to form long fibres that accumulate to become plaques. Meanwhile, other teams had identified that tangles consist of tau, a protein that usually helps to maintain the structure of nerve cells. In neurodegenerative diseases, tau moves to the wrong part of the cell, folds over on itself and forms helical filaments, which then build up as tangles.
In 1991, research supported by the MRC and other funding bodies identified the first genetic mutations to be associated with Alzheimer’s disease – and they were all in the amyloid gene. Led by Professor John Hardy, a pioneer in the field of neurodegeneration research, this work helped change our understanding of the mechanisms underpinning neurodegeneration. The MRC has funded Professor Hardy’s research at various stages of his career. Professor Hardy first became interested in studying Alzheimer’s disease during his postdoctoral research project at the MRC Neuropathogenesis Unit in Newcastle upon Tyne. He is currently at University College London heading the Department of Molecular Neuroscience, which has received approximately £6m in MRC funding since 2007.
In the late 1990s, researchers also began to identify the genetic mutations associated with tau proteins and their role in forming tangles in neurodegenerative diseases. Professor Michel Goedert at the MRC Laboratory of Molecular Biology played a fundamental role in advancing our understanding of this process. His research showed that the brain actually contains six different versions of the tau protein, all generated from a single tau gene. These different versions are all incorporated into coiled filaments within the neuronal extensions, resulting in the tangles that are observed in brains with neurodegenerative disease. In addition, Professor Goedert showed that these tau proteins have an abnormal pattern of molecular tags that reduce their ability to bind to the structural components within neurons; thus preventing tau proteins from stabilising these components. As a result, these defective tau proteins lead to the formation of tangles that then lead to eventual neurodegeneration. Professor Goedert was also amongst the first to report a mutation in the tau gene in an inherited dementia, which firmly establishes that tau pathology is central to the neurodegenerative process.
This research highlights how our understanding of the fundamental processes of neurodegeneration has evolved.
Image description: Left: High magnification micrograph of brain tissue showing amyloid plaques (brown) as seen in Alzheimer disease. Centre: Gene sequencing results from Professor Hardy’s research in the 1990s showing a mutation in the beta amyloid gene that contributes to Alzheimer’s disease. Right: Professor Hardy at the 2015 Breakthrough Prize Ceremony.
Professor Hardy receiving his Breakthrough Prize from Anne Wojcicki (founder, 23andme) and Sergey Brin (co-founder, Google) at the 2016 Award Ceremony.