New understanding of how Alzheimer’s develops

Alzheimer’s Disease (AD) is the most common form of dementia, with symptoms that include gradually worsening memory loss and confusion. While there is no cure at present, a project funded by the European Research Council has opened up new research avenues that could one day lead to new therapeutic applications.

“Scientists have begun to better understand the genetics behind AD,” says MIRNA_AD project coordinator Bart De Strooper from VIB in Belgium. “For example, some 25 genes have been identified that we now know influence the genetic risk of developing the disease. We also know that amyloid peptides (a type of amino acid) are the main component of the amyloid plaques found in the brains of Alzheimer patients.”

Scientists believe that this plaque build-up blocks cell-to-cell signalling and could trigger inflammation. “What we don’t know, however, is exactly how Alzheimer’s progresses,” he adds.

Understanding disease pathways

De Strooper argues that the conventional focus on targeting amyloid peptides has been too simplistic. “It is based on the prediction that if you take away the amyloids, then you’ll have the cure,” he says. “The truth is that the development of AD is far more complex. It is not like killing the microbe that gives you pneumonia; AD involves a series of abnormal processes in the brain. What is needed is a new, non-linear way of thinking about how actions and reactions in the brain contribute towards the development of AD. We know now, for example, that abnormalities in amyloids start decades before the disease develops.”

The ERC grant enabled De Strooper to think outside of the box, and as a result make some important discoveries. “Our overall focus was on identifying pathways in the development of Alzheimer’s,” he explains. “We began by looking at both proteins and non-coding RNA (molecules involved in various biological roles in the expression of genes, but which are not translated into proteins), and examined the role that non-coding RNA might play in the development of AD.”

Potential therapeutic targets

The project was able to characterise important changes that take place in RNA in the brain of AD patients. In particular, De Strooper and his team identified several specific RNA molecules that changed significantly, such as the molecule micro-RNA 132. The next stage was then to investigate how these changes affect the brain in AD patients.

 “By studying these micro-processes, we have arrived at a broader view of how AD develops, and achieved a broader understanding of what is going on in the brains of patients,” says De Strooper. “We now know that certain micro-RNAs regulate the amyloid and the Tau pathway together and could have an influence in inflammatory aspects of AD.”

These discoveries have opened up new research avenues. De Strooper is currently exploring whether micro-RNA molecules could be a potential target for therapeutic drugs, through studying the effect of manipulating these micro-RNA in mice. “It is perhaps a little early to say, but I think this research has the potential to be spun off one day and commercialised.”

The project has also underlined the complexity of Alzheimer’s, and the need to take a more holistic approach to research. “This is really where the ERC grant came into its own,” says De Strooper. “It can be difficult to get funding for this type of project, because they are seen as too speculative and risky. But the ERC is all about removing barriers and taking risks. The grant enabled me to carry out complex and efficient research, and I was able to train people who have since gone on to take up excellent positions.”