According to the World Health Organization, Alzheimer’s disease is the most common cause of senile dementia that affects dozens of millions of people worldwide, with numbers expected to double every 20 years if more effective treatments are not forthcoming.
It has long been thought that Alzheimer’s disease is caused by the build-up of amyloids and certain proteins, especially a group thereof known as tau. However, the process whereby the build-up occurs and begins to encroach upon surrounding tissue has remained a mystery.
Luckily, researchers from Tokyo Metropolitan University have recently discovered a mechanism by which clumps of tau protein are created in the brain, eventually leading to the death of brain cells and Alzheimer’s disease.
The mechanism was found to be triggered by a specific mutation to an enzyme called MARK4 (Microtubule Affinity Regulating Kinase 4) that changed the properties of tau – normally an important part of cell structure known as the cytoskeleton – making it more insoluble and more likely to aggregate.
In healthy people, to keep the microtubules (or the “arms” of the cytoskeleton) constantly building and disassembling, MARK4 helps tau detach from the arms of this structure. Yet given a certain mutation in the gene that provides the blueprint for making MARK4, tau starts to build-up, resulting in impairments to memory and motor functions.
While previous work had already associated this with an increased risk of Alzheimer’s, prior to the new findings it wasn’t know why it might be the case.
In the study, a research team led by Associate Professor Kanae Ando of Tokyo Metropolitan University had introduced mutations into transgenic drosophila fruit flies that also produce tau and observed the changes.
What they found was that the mutated tau not only contained an excess of certain groups of chemicals that cause it to misfold, but also lost a great deal of its solubility, which makes it much easier for it clump and aggregate in brain tissue.
Since MARK4 is known to be involved in other diseases caused by tau abnormalities, the new findings could eventually bring about new preventative measures and treatments for a range of neurodegenerative conditions in addition to Alzheimer’s.