Explainer | Unravelling 2 Alzheimer’s markers: what are amyloid plaques and tau tangles, how do they form and what do they do to the brain?
- People with Alzheimer’s disease have amyloid plaques and tau tangles in their brains. These are caused by build-ups of proteins that block electrical messages
- Techniques developed recently have shown these protein build-ups in action, changing from liquid to solid, offering new information about the process
Amyloid plaques and tau tangles are telltale signs of Alzheimer’s disease – you hear the phrase all the time in connection with dementia, but what are they?
Neurologist Dr Andrew Lees, a professor of neurology at the National Hospital in London and University College London and an expert on neurodegenerative diseases, explains the way plaques and tangles work.
The plaques consist of dense, insoluble clumps in the spaces between the nerve cells, or neurons, in the brain. They prevent the brain’s messages from getting through effectively or – eventually – at all. They are composed of beta-amyloid, a protein.
Tangles are the result of a build-up of tau protein inside neurons. In a healthy brain, tau binds with the neurons’ internal structures, microtubules, which help disperse nutrients throughout the neuron.
As Alzheimer’s progresses, the tau sticks to other tau proteins, forming long protein threads of tau inside the neurons – tangles – and ultimately, these interfere with the neuron’s ability to function.
The synaptic communication necessary for healthy cognition is hijacked.
In my mind’s eye, I see something cobwebbed, clogged, matted: nothing’s getting through that mess.
He says the phrase was his “attempt to describe what a large number of amyloid plaques resemble under a microscope; sepia because the first stain used to clearly demarcate them was Congo red and the plaques stained red”.
Seen through a microscope, plaques “are dense roundish insoluble clumps in the spaces between the nerve cells that contain the protein beta amyloid”, he says.
“Tangles are more wispy, some are flame-shaped and contain the protein tau in a form which causes the fibres inside it to twist” like a helix. He sends a photo: sepia-stained clusters like old blood, and a litter of black tangles knotted across one another.
Recently, biomedical engineers at the University of Sydney in Australia, working with scientists at Harvard University in the United States and Cambridge University in the UK, developed sophisticated techniques to observe closely the ways in which these proteins gather and ultimately cause catastrophic and irreversible damage.
So what have they discovered – where do these proteins start and how do they build up in the brain as solids?
Proteins are found inside cells in the human body and are critical for many healthy functions, explains Daniele Vigolo, a researcher at The University of Sydney.
A typical healthy behaviour for proteins inside cells, he says, is to form small droplets of concentrated proteins called biomolecular condensates. In a healthy individual, these liquid droplets keep forming and dissolving inside cells. They are used in many regular cellular activities, such as information transfer and communication.
The team’s study focused on a protein called “fused in sarcoma” (FUS). It is found, together with many other proteins, inside brain cells such as neurons.
One of the issues in neurodegenerative disease, Vigolo says, is the transition of these protein droplets from liquid to solid. When the solid proteins cannot revert to liquid, the healthy functions of the cell are lost or compromised.
If this happens in a neuron cell, he says, it can lead to a neurodegenerative disease.
In the study, he says, they were able to monitor the change in these proteins from liquid to solid, and to study their internal structure.
To do this, his team developed two new advanced optical techniques, including “spatial dynamic mapping”, to witness the transition at a cellular level over time.
“This is a huge step forward towards understanding how neurodegenerative diseases develop,” said Vigolo’s colleague Dr Yi Shen, lead author of the published research.
Their research results, Vigolo says, will also help in understanding the basic behaviour of proteins, to potentially help in monitoring the disease.
They could also contribute to identifying a new treatment in the future.
