The study, published in the journal Science, used yeast to unravel how the genes affect cells in the brain. It is the first study to show that the risk genes affect a hallmark protein in Alzheimer’s called amyloid, paving the way for the next steps in treatment development.
Over the last decade, scientists have been working to identify genes which could influence a person’s risk of developing Alzheimer’s. Two breakthrough studies co-funded by Alzheimer’s Research UK identified nine genes which were associated with Alzheimer’s, but their exact function in Alzheimer’s remained unclear.
The new study from Massachusetts Institute of Technology has uncovered important clues about the roles of the risk genes by using a basic model of Alzheimer’s in yeast. This simple and effective method could revolutionise the way future gene discoveries are investigated.
The scientists introduced the amyloid protein into yeast. Amyloid is known to build up in toxic clumps in the brain during Alzheimer’s and is one of the characteristic features of the disease. They discovered that amyloid was disrupting a vital process in yeast called endocytosis- which transports important molecules into and around the cell.
The researchers expressed the Alzheimer’s risk genes in their yeast model, and in more complex models using worms and rat brain cells. They found that a number of the genes, including one called PICALM, could influence amyloid’s ability to disrupt endocytosis. It provides a previously unknown link between the genes and the amyloid protein, and sets a new direction for treatment research.
Prof Julie Williams of Cardiff University is Chief Scientific Adviser to Alzheimer’s Research UK and led the initial studies which identified the Alzheimer’s risk genes in humans. She said:
“In 2009 we discovered that the gene PICALM affected the risk of developing Alzheimer’s disease. We have since identified a further three genes which, together with PICALM, show for the first time that the process of endocytosis may play an important role in Alzheimer’s. This study now brings the pieces of the puzzle together and shows that PICALM influences the damaging effects of amyloid.
“Our genetic discoveries are now pinpointing new disease mechanisms which can lead to the development of new treatments. This is enormously exciting and underlines the importance of understanding more about the genetics of Alzheimer’s disease.”
Dr Marie Janson from Alzheimer’s Research UK, said:
“We are very excited by these promising results which offer new hope for treatment development. The study shows how research performed in the UK can have real impact in the scientific community world-wide. It is very encouraging to see that work funded by Alzheimer’s Research UK has formed the basis for this work and that real progress is being made to discover how these Alzheimer’s risk genes could help in the search for new treatments.”
“There are over 500,000 people in the UK alone living with Alzheimer’s disease and this figure is expected to rise significantly. Dementia research is currently hugely underfunded and we must invest now if we are to capitalise on encouraging early findings.”
Alzheimer’s Research UK