Exact Moment a Tau Protein Starts to Become Toxic
Alzheimer’s Disease is characterized by Amyloid plaques and tangles, which are basically a bunch of proteins that are folded into a shape allowing multiple copies of the protein to stick together. Interestingly, a new study states that they have discovered the precise moment that these proteins start to become neurodegenerative.
Even though over half a million people in Canada suffer from Alzheimer’s Disease, and billions of dollars are spent on treatments and clinical trials, it is still one of the most puzzling diseases out there. It is the most common cause of dementia, and patients experience severe memory loss and difficulties with other cognitive abilities interfering with their daily life.
The protein tangles that are found in the brains of patients are twisted fibres of the proteins. The “tau” protein is one of the main components of the tangles and aggregate formation, such that people with more severe dementia seem to have a greater build-up of this protein in their brain.
It isn’t known how or why these proteins shape, fold and build-up into these tangles, but we do know that this process begins with a pathogenic “seed”. This seed serves as a template for fibril growth.
Using a technology called mass spectrometry, researchers from UT Southwestern Medical Centre were able to measure tiny changes in the tau protein, as it folds and shapes itself. They studied both “good” and “bad” forms of the protein in hopes of figuring out what makes them become a tangle.
All proteins are made up of a string of amino acids and are then folded into their functional shape. By coiling and folding into a 3D shape, they can perform their biological purpose. However, if they are improperly folded or not even folded at all, they can be dysfunctional or toxic.
They discovered that in the good forms of the protein, the portions that allow it to stick to itself are hidden inside. Looking at the bad forms, they saw that the “sticky parts” are on the outside allowing it to build upon itself, becoming toxic. This shape-shifting process is the moment when the tau protein either becomes good or bad.
The researchers suggest that this work might translate to other proteins and could possibly lead to a better understanding of the neurodegenerative process. If the shape-shift can be detected early enough, better treatments can be put in place even before Alzheimer’s symptoms are experienced.
“The hunt is on to build on this finding and make a treatment that blocks the neurodegeneration process where it begins. If it works, the incidence of Alzheimer’s disease could be substantially reduced. That would be amazing.” – Dr. Diamond Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases
They are optimistic, as a recently approved drug called, Tafamidis, stabilizes another type of shape-shifting protein called transthyretin, which builds up in the heart, similar to tau building up in the brain. But they stress that there is still a long way to go, their next step is to try a simple test, examining a patient’s blood or spinal fluid to see if the abnormal tau protein can be detected.