Alzheimer’s disease and other types of dementia have been one of the deadliest killers in the Western world for decades. Alzheimer’s is currently sitting at #6 in the Top 10 causes of deaths in the U.S. Yet, good news might be on the horizon.
Researchers from Tokyo Metropolitan University have discovered a new mechanism by which clumps of tau protein are created in the brain, killing brain cells and causing Alzheimer’s disease.
A specific mutation to an enzyme called MARK4 changed the properties of tau, usually an important part of the skeletal structure of cells, making it more likely to aggregate and more insoluble.
Getting to grips with mechanisms like this may lead to breakthrough treatments.
Alzheimer’s is said to be caused by the build-up of tangled clumps of a protein called “tau” in brain cells.
These sticky aggregates cause neurons to die, leading to impairment in memory and motor functions. It is not yet clear how and why tau builds up in the brain cells of Alzheimer’s patients.
Understanding the cause and mechanism behind this unwanted clumping would open up the way to new treatments and ways to prevent the disease.
MARK4 Enzyme Mutation
In the study, the researchers explored the role played by the MARK4 (Microtubule Affinity Regulating Kinase 4) enzyme in Alzheimer’s disease.
When everything is working normally, the tau protein is an important part of the structure of cells, or the cytoskeleton.
Problems start when a mutation occurs in the gene that provides the blueprint for making MARK4. The process looks something like this:
- A mutation in the gene that governs the production of MARK4 causes the production of dysfunctional MARK4 enzymes.
- The “bad” MARK4s start promoting “tau aggregation” and cause the tau proteins to start building up instead of doing their job.
- The tau buildup prevents the healthy development of brain cells and leads to the death of neurons, i.e. Alzheimer’s disease.
Previous work had already associated this MARK4 mutation with an increased risk of Alzheimer’s, but it was not known why this was the case, until now.
For the study, the team from Japan introduced mutations into transgenic drosophila fruit flies that also produce human tau, and studied how the proteins changed.
They discovered that this mutant form of MARK4 makes changes to the tau protein, creating a pathological form of tau. Not only did this “bad” tau have an excess of certain chemical groups that caused it to misfold, they found that it aggregated much more easily and were no longer soluble in detergents.
This made it easier for tau to form the tangled clumps that causes neurons to degenerate.
MARK4 has also been found to cause a wide range of other diseases which involve the aggregation and buildup of other proteins. That’s why the team’s insights into tau protein buildup may lead to new treatments and preventative measures for an even wider variety of neurodegenerative conditions.
What does this mean for us?
As of right now, this discovery is crucial mostly for the scientists looking for Alzheimer’s treatments and prevention methods. For the rest of us, it’s just a glimpse of hope that the ongoing nightmare of this brain disease may be coming to an end. Or, at least that future generations might be spared.
In the meantime, things like staying mindful about the connection between Alzheimer’s and diabetes or Alzheimer’s and dental hygiene remains crucial. Whatever we say about Alzheimer’s and dementia, these are slow-progressing diseases and take years and decades of development before their first symptoms even appear.
So prevention is of the utmost importance.