Alzheimer’s research: Christian Haass receives ‘Brain Prize’
Denmark's Lundbeck Foundation honors Munich researcher – together with colleagues in the UK and Belgium – for his groundbreaking work on the genetic and molecular bases of Alzheimer's disease.
Four neuroscientists working in the UK, Belgium and Germany have won the world's most valuable prize for brain research. Among the awardees is Professor Christian Haass, Chair of Metabolic Biochemistry at Ludwig-Maximilians-Universitaet (LMU) in Munich and Spokesperson for the German Center for Neurodegenerative Diseases (DZNE) in Munich. The 2018 Brain Prize also goes to Professors Bart De Strooper (London and Leuven), Michel Goedert (Cambridge) and John Hardy (London). All four scientists are honored for their groundbreaking research into the genetic and molecular bases of Alzheimer's disease.
The Brain Prize, awarded by the Lundbeck Foundation in Denmark, is worth one million euros. Awarded annually, it recognises one or more international scientists who have made distinguished contributions to neuroscience.
The research pioneered by these four European scientists has revolutionised our understanding of the changes in the brain that lead to Alzheimer´s disease and related types of dementias. Around 10 million people in Europe suffer from Alzheimer's disease. Alzheimer's and other neurodegenerative diseases of the ageing brain cause a great deal of suffering for patients and their families, and present a huge challenge for society. They are among the most difficult diseases to understand, in spite of the dramatic progress made over the past several decades. This year's Brain Prize winners have, individually and together, made essential contributions to the genetic and molecular knowledge of Alzheimer's disease upon which the search for new ways to diagnose, treat and possibly even prevent it and other devastating diseases of the ageing brain, are based.
"The Brain Prize is an ambassador for science and puts a spotlight on great discoveries," Christian Haass said, "We are facing a time when more and more people don't believe in science anymore. Science is not always right, but it is the only way to go to find the truth and for humans to progress." When Haass began to work on Alzheimer's disease in 1990, very little was known about the cellular mechanisms involved in this disease. He focused on the generation and metabolism of amyloid, the major component of the plaques that are a hallmark of the disease.
His research into Alzheimer's has focused on "the cascade of events that begins with amyloid and progresses through the development of plaques and tangles, which eventually kill brain cells and destroy memory," he said. Haass hypothesised that amyloid production may occur normally and may not necessarily be part of a pathological process, a suggestion which was at variance with the widely accepted general opinion in the field at the time. This pivotal finding was highly significant, and has since led to the development of therapies to lower amyloid production in patients. Working with John Hardy, Professor Haass demonstrated how amyloid is generated and how genetic mutations seen in families with very aggressive and rare forms of Alzheimer's affect its production.
Most recently, Professor Haass has generated mouse models to investigate inflammation in neurodegenerative disorders, which according to his findings may at least initially play a protective role. He found that genetic mutations alter the function of special immune cells called microglia in the brain that can lead to Alzheimer's disease. This has stimulated a completely new approach to designing possible new therapies by modulating the activity of microglia.
The other awardees:
Professor Bart De Strooper is the Director of the UK Dementia Research Institute, at University College London, and Professor of Molecular Medicine at KU Leuven and VIB, Belgium where he carried out the research that earned him his share of the Brain Prize. Professor De Strooper discovered that presenilin is a protein that 'cuts' other proteins into smaller pieces which is an important and complex process in normal cell signalling (the communication between cells). Mutations in the presenilin genes cause Alzheimer's disease. He found that these mutations lead to the production of abnormal amyloid which is the main constituent of the plaques in the brains of patients with Alzheimer's disease. He has deciphered in great detail what the mutations are doing and how they drive the disease process. Working with transgenic animals, zebra fish and human brain tissue donated by patients, Professor De Strooper applies information from genetic studies of Alzheimer's and Parkinson's disease for theories of the cellular basis of dementia to identify new drugs in collaboration with the pharmaceutical industry. "Treating amyloid very early on could provide protection against the symptoms of Alzheimer's in later life. But we have a 'catch 22 situation' in that we cannot do experiments in healthy people," said Professor De Strooper.
Professor Michel Goedert is a Programme Leader at the Medical Research Council Laboratory of Molecular Biology in Cambridge and an Honorary Professor at Cambridge University. His work using human brain tissues, transgenic mice, cultured cells and purified proteins was instrumental in the discovery – despite considerable initial scepticism – of the importance of Tau protein for Alzheimer's disease. When Tau acts abnormally, it assembles into clusters of filaments and becomes insoluble. A pathological pathway leading from soluble to insoluble filamentous Tau is believed to cause neurodegeneration. Different Tau filaments are associated with distinct neurodegenerative diseases, including Pick's disease and progressive supranuclear palsy, where Tau filaments form in the absence of beta-amyloid deposits outside brain cells. In his more recent studies, he showed that filamentous Tau clusters can propagate along nerve cell pathways through self-seeding. "Eventually – perhaps decades after seed formation – the first disease symptoms appear", said Professor Goedert. "Therefore, if you can halt propagation, that could lead to ways to prevent and treat disease."
Geneticist Professor John Hardy is Chair of Molecular Biology of Neurological Disease at the Institute of Neurology, University College London. After finding mutations in the gene for the protein, amyloid, in a family with early onset disease he proposed a ground-breaking 'amyloid hypothesis' for Alzheimer's disease suggesting that disease was initiated by the build-up of this protein in the brain. The disease progresses when there is an imbalance in the production and the clearance of amyloid. His discoveries of genetic mutations have had a dramatic impact on understanding not only Alzheimer's disease but more recently in other neurodegenerative diseases including Parkinson's disease, progressive supranuclear palsy and motor neuron disease. With his collaborators, their development of transgenic mice that mimic these diseases process has provided the foundation of clinical trials for drugs to treat these complex diseases. "Collaborating with clinicians, geneticists and cell biologists is work in progress. Although we have not found a successful treatment yet, I believe we are on the way towards rational, mechanism-based treatments," said Professor Hardy. His work on Alzheimer's disease, other dementias and Parkinson's disease is amongst the most highly cited in neuroscience.
This year's award represents an array of European countries: UK, Belgium, Germany and Luxembourg. All four neuroscientists were honoured – and surprised – to receive the 2018 Brain Prize and said how important Alzheimer's research is in the vastly diverse field of neuroscience.
"The Brain Prize recognises that basic science makes a real contribution, even though much of it cannot be directly applied to clinical care," said Professor De Strooper. "The Prize is an important sign for young scientists to know that they can still make big discoveries, and that we urgently need them to pursue research into diseases of the ageing brain."
"At a time when there is disappointment about the lack of an effective treatment for Alzheimer's disease, it seems clear that we need to have a more detailed understanding of the mechanisms of disease," said Professor Goedert.
Professor Hardy said, "In the early 1980s, research into Alzheimer's disease was a real backwater. The first conference only attracted 40 people, but now thousands attend. The pace of knowledge is very fast and the quality of science is excellent. Finding out about the interactions of the different types of cells in the brain is fundamental to our understanding of how the brain works."
The chairman of the Lundbeck Foundation Brain Prize selection committee, Professor Anders Bjorklund, said, "Alzheimer´s disease is one of the most devastating diseases of our time and the remarkable progress that has been made during the last decades. These four outstanding European scientists have been rewarded for their fundamental discoveries unravelling molecular and genetic causes of the disease that have provided a basis for the current attempts to diagnose, treat and possibly even prevent neurodegenerative brain diseases. The award recognises that there is more to Alzheimer´s disease than amyloid, and that the field of dementia research is more than Alzheimer´s disease alone."
The Lundbeck Foundation Brain Prize:
The one million Euro Brain Prize is awarded by the Lundbeck Foundation in Denmark. In 2018, the Prize will be awarded for the eighth consecutive year. The Brain Prize is a personal prize, awarded to one or more scientists who have achieved distinction through outstanding contributions to brain research. More information can be found on The Brain Prize website, http://www.thebrainprize.org The Lundbeck Foundation is one of the largest, industrial foundations in Denmark with a market value of more than DKK 60 billion. The Lundbeck Foundation annually grants approx. DKK 500 million in support of Danish-based, biomedical research of the highest, international quality with a special focus on brain health as part of the foundation's vision to create better lives through new knowledge, http://www.lundbeckfonden.com
As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 16 percent of LMU's 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU's designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research.
The German Center for Neurodegenerative Diseases (DZNE) is a research institute dedicated to dementia. A member of the Helmholtz Association and first of six German centers for health research (DZG), the DZNE was established by the Federal Ministry of Education and Research. http://www.dzne.de
The national UK Dementia Research Institute was established in 2017 by the Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. The £250million institute will accelerate discoveries to prevent, treat and care for people with all types of dementia, and it will help us understand ways to keep the brain healthy. http://www.ukdri.ac.uk
The Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge is a research institute dedicated to the understanding of important biological processes at the levels of atoms, molecules, cells and organisms. In doing so, we provide knowledge needed to solve key problems in human health. www2.mrc-lmb.cam.ac.uk
Alzheimer's disease is the most common type of dementia. It is a progressive condition, which means the symptoms develop gradually and become more severe over the course of several years. It affects multiple brain functions. The first sign of Alzheimer's disease is usually minor memory problems. As the condition develops, memory problems become more severe.
Alzheimer's disease is caused by parts of the brain shrinking (atrophy), which affects the structure and function of particular brain areas. In the brains of people with Alzheimer's disease, scientists have found amyloid plaques (abnormal deposits of protein), neurofibrillary tangles (containing tau) and imbalances in a chemical called acetylcholine.