Super-resolution microscopy sheds light on how dementia protein becomes dysfunctional

UQ Queensland Brain Institute’s Clem Jones Centre for Ageing and Dementia Research Professors Frédéric Meunier and Jürgen Götz found a protein, Tau, involved in Alzheimer’s disease affects the organisation of the signalling protein Fyn, which plays a critical role in memory formation.

“One of the distinguishing features of Alzheimer’s disease is the tangles of Tau protein that form inside brain cells, but this is the first time anyone has demonstrated that Fyn nanoclustering is affected by Tau,” Professor Götz said.

Professor Meunier said single molecule imaging in living brain cells allowed unprecedented access to the organisation of key proteins in small nanoclusters that were not detectable previously.

“We have shown that Tau controls the Fyn nanoclustering in dendrites, where the communication between brain cells occurs,” Professor Meunier said.

“When Tau is mutated, Fyn makes aberrantly large clusters, thereby altering nerve signals and contributing to dysfunction of the synapse-junctions between nerve cells.”

Professor Meunier’s team used the super-resolution single molecule imaging technique to see how Tau and its mutants control Fyn nanoclustering.

Professor Meunier went on to investigate a different mutant of Tau found in families with a very high risk of developing frontotemporal dementia and found that Fyn was over-clustered in the spines of dendrites.

“Imagine that you have clustering of Fyn, a signalling molecule, throughout your life; it’s going to give rise to an over-signalling problem — this could be one of the ways in which Fyn is toxic to cells,” he said.

“The spines of the dendrites are critical to how nerve cells communicate with each other and underpin memory and learning.”

Exactly what causes Alzheimer’s and other forms of dementia is still a mystery, but Fyn is linked to both the plaques of amyloid protein that form between brain cells, and tangles of Tau protein that form inside brain cells — two distinguishing features of Alzheimer’s disease.

“Super-resolution single molecule imaging gives us an unprecedented insights into what is happening in living nerve cells, with the aim of understanding the biology behind these complex and debilitating diseases,” Professor Meunier said.

Top Articles

Sharp increase in falls in women during midlife

Falls are not just a problem of advanced age, according to researchers, who have identified a sharp increase in falls after the age of 40, particularly in women.

Read More

Parasitic worms cause cancer — and could help cure it

Billions worldwide are infected with tropical worms. Unsurprisingly, most of these people live in poor countries, kept poor by the effects of worm-related malnourishment. What may surprise many is that worms also cause the majority of cases of some cancers in these countries.

Read More

Phytochemicals: beyond vitamins

Phytochemicals are non-nutritive chemicals in plant foods that protect plants from microbial invasions and infections.

Read More

Latest News

Standard pathology tests outperform molecular subtyping in bladder cancer

While trying to develop a comparatively easy, inexpensive way to give physicians and their patients with bladder cancer a better idea of likely outcome and best treatment options, scientists found that sophisticated new subtyping techniques designed to do this provide no better information than long-standing pathology tests.

Read

Have your health and eat meat too

Barbecued, stir-fried or roasted, there’s no doubt that Aussies love their meat. Consuming on average nearly 100 kilograms of meat per person per year, Australians are among the top meat consumers worldwide. But with statistics showing that most Australians suffer from a poor diet, and red meat production adding to greenhouse-gas emissions, finding a balance between taste preferences, environmental protection, and health benefits is becoming critical.

Read

Cancer patients are at higher risk of dying from heart disease and stroke

The largest and most comprehensive study looking at deaths from cardiovascular disease among patients with 28 types of cancer with over 40 years of data has shown that more than one in ten cancer patients do not die from their cancer but from heart and blood vessel problems instead.

Read

“Our bodies are our gardens - our wills are our gardeners.”

William Shakespeare