Scientists discover how Alzheimer’s disease may progress in the human brain

Tau Protein Buildup Image
Image: Thomas E. Cope et. al.

Alzheimer’s disease is quickly becoming one of the most pressing medical conditions in the world. As of 2017, it was estimated that 47 million people had the neurodegenerative disorder that typically affects older individuals. This number is expected to reach 76 million by 2030 as the number of people living over the age of 65 increases.

Those with the disease exhibit a range of symptoms starting with short-term memory loss and, in most cases, ending with life-threatening dementia. Even though this emotionally, physically, and economically taxing disease is growing in prevalence, there are currently no cures or effective treatments available.

A major reason for the lack of effective treatment options is because relatively little is known about the cause and spread of Alzheimer’s disease. There are currently two dominant theories about how the disease progresses, both involving abnormal proteins found in those with the disease.

One theory is that Alzheimer’s disease is the result of a protein called beta-amyloid building up in the brain. When beta-amyloid, a sticky plaque-like protein, builds up in our brains, it inhibits how efficiently our brains can function. If we think of our brains as high-powered machines, then beta-amyloid is the build-up of grease around the machine slowing it down.

The other theory involves a protein called tau. Tau proteins act similarly to beta-amyloid. However, instead of building up around the brain to slow it down, tau proteins do so inside the brain cells. These brain cells, called neurons, are what connect different areas of our brains and allow us to process thoughts. Therefore, when tau proteins build up inside of our neurons it is detrimental to our brain’s ability to function.

Which theory is responsible for Alzheimer’s disease has been hotly debated. Unfortunately, until we understand how the disease affects a patient, it is unlikely that we will develop better treatment options.

However, a new study conducted by researchers at the University of Cambridge has now found evidence that in the brains of humans with Alzheimer’s disease, tau proteins spread from one region of the brain to another. These findings support the notion that tau proteins may be the leading cause of the disease and give insight into how the disease progresses.

This proliferating of tau was observed in mice in a previous study where brains of healthy mice were injected with the abnormal human tau proteins. However, this new study, published in Brain, confirms for the first time that a similar process occurs in humans.

The study was conducted through two different brain-imaging techniques. First, brain scans were used to identify where in the brain the tau proteins were and how much was present. Next, the researchers observed the activities between different regions of the brain to determine which areas were connected.

When used together, these imaging techniques allowed the researchers to see if there was a link between how much tau protein had built up and brain connectivity. Remarkably, the study found that tau proteins were more abundant in parts of the brain that were strongly connected to other brain regions, implying that tau proteins travel from neuron to neuron throughout the brain.

The researchers noted in an article how the spread of tau proteins is analogous to the spread of the flu, “In a flu epidemic, people with a large number of social contacts are most likely to become infected and then to pass the infection on to others. Similarly, the transneuronal spread hypothesis predicts that strongly connected brain regions will accrue most tau”.

Furthermore, the researchers found that patients in later stages of Alzheimer’s disease, therefore with more tau protein build-up, had less connected brain regions. The connections that remained were weaker and more random as the disease progressed. This confirms that tau proteins must be a causal factor in the development of Alzheimer’s disease.

The research admittedly had some limitations. In particular, the study was cross-sectional, meaning the images were taken at one specific point in time and had a sample size of just 17 patients. The researchers are currently planning larger, long-term studies that will better confirm that the tau proteins are spreading neuron to neuron as Alzheimer’s disease progresses.

Despite the limitations of the study, the findings provide insight into novel treatment options. The development of a drug that prevents the spread of these tau proteins, restricting them to just those brain cells already affected, could stop the spread of Alzheimer’s disease in its early stages.






Author: Skylar Knight

Skylar is currently in the MSc Science Communication program at Imperial College London. He has years of experience working in science museums, academic publishing, writing, filmmaking, and science education.