A look at Tau: Understanding a critical protein that contributes to Alzheimer’s disease

03/11/2021

It may be unfamiliar to most people, but a protein called tau could hold the key to changing the course of Alzheimer’s disease (AD). This is why TauRx, an Aberdeen-based global leader in tau-based Alzheimer’s disease research, has dedicated its research programme to the role of this protein in AD and other related conditions. 

Every 3 seconds, someone somewhere in the world develops Alzheimer’s, the most common form of dementia. It is predicted that a staggering 132 million will be diagnosed by 2050. As one of the world’s greatest unmet medical needs, an effective treatment to slow or halt the disease is desperately needed. 

What is tau and what happens to it in Alzheimer’s? 

Tau protein is mainly found in our brain cells, called neurons. In healthy brains, the tau protein performs several vital roles. One of the most important is stabilising the microtubules in brain cells – effectively supporting the scaffolding structure of our neurons which allow nutrients and neurotransmitters to pass through them. Delivery of neurotransmitters to the synapses (or junctions between these cells) is necessary for signals to pass through the brain. 

In the human body, healthy proteins are designed to fold into precise three-dimensional structures, allowing them to interact in particular ways to carry out their functions. In Alzheimer’s, waste material in cells can induce the tau protein to misfold. This misfolded form can then attract other tau proteins to misfold and stick together. These clumped forms can spread between cells and ultimately form bundled tangles, which eventually cause the death of neurons and the cognitive and functional decline that characterises AD.

Research has revealed that this abnormal tau accumulates, or aggregates, in the specific regions of the brain that are involved in memory. 

What can be done to stop the harmful tau? 

Discovering an effective and safe way of breaking down the tangles of tau protein could represent a major breakthrough in the treatment of Alzheimer’s disease. TauRx was founded in 2002 based on key discoveries made by its CEO, Professor Claude Wischik, including that of an experimental chemical compound capable of dissolving these. 

Compounds capable of interfering with the aggregation of tau proteins are known as “tau aggregation inhibitors”, which work by breaking down the tau clumps and/or preventing further tau proteins from binding and misfolding. Therefore, they help prevent the build-up of the toxic tangles in the brain.   

When does the tau pathological process start? 

Studies have established that the disease process may start around 20 years prior to any symptoms showing, which supports the drive towards protecting brain health and the prospect of one day developing preventative treatments. 

The link between tau and symptoms of dementia

We know from research that the amount of pathological tau in the brain correlates well with the level of clinical decline seen in a person with AD. Put simply, the more “bad” tau there is, the more affected a person is by symptoms of dementia. Therefore, tau is considered to be an important target for a treatment.  But over the last 20 years, clinical research had focused mainly on another brain protein associated with Alzheimer’s and dementia, called beta-amyloid. Unlike tau, beta-amyloid builds up outside and between the neurons in the form of senile plaques, a type of lesion. In contrast to tau, research suggests little correlation with the functional impact of dementia and the amount of amyloid in their brains.

AD remains a complicated disease to treat, but progress is being made. The continued focus to develop new diagnostics and treatments  has the potential to transform the lives of millions of people with dementia, and the millions more who love and care for them.

Dr Sonya Miller is the Medical Oversight Lead at TauRx
TauRx is a global leader in tau-based Alzheimer’s disease research with a mission to discover, develop and commercialise innovative products for the diagnosis and treatment of neurodegenerative diseases caused by protein aggregation. They are currently working towards offering the first disease-modifying treatment targeting tau for the world’s greatest unmet medical need. Find out more at www.taurx.com

 

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