The one million Euro Brain Prize, awarded by the Lundbeck Foundation in Denmark has been announced. Last year’s winners, received the prize for their work understanding the mechanisms of reward in the brain. This year, the prize has gone to four neuroscientists for their groundbreaking research on the genetic and molecular basis of Alzheimer’s disease.

Professor Bart De Strooper : 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

: 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 Michel Goedert : Program Leader at the Medical Research Council Laboratory of Molecular Biology in Cambridge and an Honorary Professor at Cambridge University

: Program Leader at the Medical Research Council Laboratory of Molecular Biology in Cambridge and an Honorary Professor at Cambridge University Professor Christian Haass : The Ludwig-Maximilians-University of Munich and at the German Center for Neurodegenerative Diseases

: The Ludwig-Maximilians-University of Munich and at the German Center for Neurodegenerative Diseases Professor John Hardy: Chair of Molecular Biology of Neurological Disease at the Institute of Neurology, University College London

Collectively, their research has revolutionized our understanding of the changes in the brain that lead to Alzheimer´s disease and related types of dementias. Alzheimer’s disease and other neurodegenerative diseases of the ageing brain cause a great deal of suffering for patients and their families and are a huge challenge for society. It is among the hardest diseases to get a grip on despite dramatic progress over the last decades.

Professor De Strooper, in his work with transgenic animals, zebra fish and brain tissue discovered that the protein presenilin cuts other proteins into smaller pieces (called peptides). This process is important in cell signaling, that is, the transmission of signals from outside the cell into the nucleus. Mutations in presenilin genes, lead to the production of abnormal amyloid which is the main constituent of the plaques in the brains of patients with Alzheimer’s disease. Professor De Strooper stated:

“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.”

Professor Michel Goedert, in his work using human brain tissues, transgenic mice, cultured cells and purified proteins, was instrumental in the discovery of the role of the Tau protein in causing Alzheimer’s disease. When Tau acts abnormally, it assembles into clusters of filaments and becomes insoluble. When pathological, 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. Professor Goedert stated:

“Eventually – perhaps decades after seed formation – the first disease symptoms appear. Therefore, if you can halt propagation, that could lead to ways to prevent and treat disease.”

When Professor Hass started his research on Alzheimer’s disease in 1990, very little was known about the cellular mechanisms involved in Alzheimer’s disease. He hypothesized that amyloid production may be normal and not necessarily part of a pathological process — a widely accepted opinion in the field at this time. Working with Professor John Hardy, Professor Haass has demonstrated how amyloid is generated and how genetic mutations seen in families with very aggressive and rare forms of Alzheimer’s affect its production. He has found more recently, using mouse models, that inflammation in neurodegenerative disorders may be initially protective and that genetic mutations alter the function of immune cells in the brain (microglia) that can lead to Alzheimer’s disease. This has stimulated the development of new therapies which focus on the modulation of the activity of microglia. Professor Hass stated:

“My research into Alzheimer’s has focused on the cascade of events starting with amyloid and progressing through the development of plaques and tangles that eventually kill brain cells and destroy memory.”

Professor John Hardy proposed a ground-breaking ‘amyloid hypothesis’ for Alzheimer’s disease, after he found mutations in the gene for the protein, amyloid, in a family with early onset disease. He suggested that disease was initiated by the build-up of amyloid in the brain. 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. Professor Hardy stated:

“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.”

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.”

Importantly, much of this research was made possible through the use of animals for research. Such use highlights the fundamental role that animals play in the basic research process and the timescales that are relevant before such work results in application to humans.

Speaking of Research