Alzheimer’s disease affects tens of millions of people worldwide. It’s the most common cause of senile dementia. According to the World Health Organization, the number of people diagnosed worldwide could double every 20 years if left unchecked.
The life-changing, debilitating condition is caused by the buildup of tangled clumps of tau protein in brain cells that cause neurons to die. The result is an impairment in motor functions and memory.
Unfortunately, why and how tau builds up is still unclear. If researchers figure out the mechanism and cause behind this unwanted clumping, it would lead to preventative measures and new treatments against the disease. Some teams have uncovered bits and pieces of information, but not enough.
Last month, Tokyo Metropolitan University scientists discovered a new mechanism by which tangles of tau protein form in the brain. An enzyme called MARK4 (Microtubule Affinity Regulating Kinase 4) is partly responsible.
Healthy tau is an integral part of the skeletal structure of cells. They keep the microtubules (the arms of the cytoskeleton) always building and disassembling. The normal MARK4 helps tau detach from the components of this structure. But there’s a mutated version of MARK4 that makes tau aggregate and more insoluble. The researchers think that if they can control this mechanism, it may lead to breakthrough treatments.
The mutation stems from a malfunction in the gene that provides the blueprint for making MARK4. The team found that it was this mutated enzyme altering the tau protein. The discovery was made through experiments. They artificially introduced mutations to transgenic drosophila fruit flies, an insect that also produces human tau, and observed how the proteins changed in vivo.
The pathological form of tau has an excess of specific chemical groups that caused it to misfold. It also aggregates much more quickly and is no longer soluble in detergents. These characteristics make it easier for them to form the tangled clumps that cause neuron degeneration.
The team’s findings could also lead to new preventative measures and treatments for other neurodegenerative conditions because MARK4 has been found to cause other diseases that involve the aggregation and buildup of different proteins.
