This year’s one-million-euro Nobel of Neuroscience has been split among four European biologists whose research has pinned down the origins of Alzheimer’s disease.
• Michel Goedert, head of neurobiology at Cambridge University’s Laboratory of Molecular Biology.
• Bart De Strooper, director of the UK Dementia Research Institute at University College London (UCL).
• John Hardy of the UCL Institute of Neurology.
• Christian Haass of Ludwig-Maximilians University in Munich.
The foundation will make the awards at a ceremony May 9 in the Royal Danish Library Black Diamonds Building in Copenhagen.
Denmark, which is struggling with an aging population, reports around 7,500 cases of dementia every year. Almost 80,000 people have the condition, including 50,000 with Alzheimer’s. The incidence is expected to triple in the next 30 to 40 years.
Goedert, De Strooper, Hardy and Haass revolutionized scientists’ understanding of the harmful changes in the brain that lead to Alzheimer’s.
Goedert’s research led to tau protein being considered one of the most important constituents of the tangles inside Alzheimer’s patients’ nerve cells. He was instrumental in identifying the key role that tau plays in the development of the disease. His work showed that Alzheimer’s stemmed from more than just an accumulation of another harmful protein — beta amyloid.
De Strooper’s contribution was learning how secretases — enzymes that clump to form plaque in Alzheimer’s patients’ brains — are constructed and how they function. His findings led to the development of drugs that can either lower the production of, or increase the body’s clearance of, beta amyloid.
Hardy’s work focused on the genetic mutations leading to Alzheimer’s. In rare cases, Alzheimer’s is inherited. This means that people in some families have a 50 percent chance of contracting the disease from one parent. Hardy’s studies were the driving force behind the hypothesis that the accumulation of beta amyloid is the main cause of Alzheimer’s.
Haass had been studying beta amyloid since the 1990s. He discovered that it is not the result of a disease-related process but that it forms naturally from precursors. Haass also played a pivotal role in identifying and describing how secretase enzymes control beta amyloid formation. Thanks to his research, scientists know that the accumulation of beta amyloid between brain cells is due to an imbalance in the production and clearance of amyloid.
These studies all led to the formation of the widely accepted amyloid hypothesis. It posits that beta amyloid clumping in the brain is the key to the development of Alzheimer’s.
Amyloid protein is a normal constituent of the surface membrane of the brain cell. Secretases break it into fragments. And one of these fragments, beta amyloid 42, has a tendency to accumulate in clusters between brain cells. This makes it a significant marker of the disease.
Scientists came up with the hypothesis after studying the inherited form of the disease. It was based on their observation that the mutations of the three genes that lead to early-onset Alzheimer’s also result in over-production of toxic beta amyloid in the brain.
Another classic characteristic of Alzheimer’s is neurofibrillary filaments. They are formed by tau protein that would normally play a key role in the formation of brain cell structures. In Alzheimer’s, neurofibrillary filaments are destroyed and fibrous clumps or tangles are formed.
While beta amyloid plaque is found between brain cells, tau tangles are found inside the cells. Tangles usually appear in the part of the brain associated with memory. They spread to other areas of the brain as the disease progresses.
All four prize winners increased scientists’ understanding of both the genetics and molecular mechanisms of Alzheimer’s and other neurodegenerative disorders. And their work has already led to the development of new treatment candidates.
The Lundbeck Foundation facilitates collaboration in neuroscience research by organizing lectures, conferences, meetings and workshops with brain researchers, as well as awarding the annual Brain Prize.