Invisible illness – this is how various mental conditions are sometimes described. For example, you cannot really see dementia. Or can you? Scientists from the University of Queensland used super-resolution microscopy to see key molecules in living brain cells. This may help understanding memory formation and the mechanisms of dementia.
Illustration of dementia from 1896 – with ageing population age-related dementia is going to be a bigger problem. Image credit: Wellcome Collection gallery via Wikimedia (CC BY 4.0)
One of the most common causes of dementia is Alzheimer’s disease. Scientists know that one of the distinctive characteristics of of Alzheimer's disease is the tangles of Tau protein that form inside brain cells.
However, scientists are not entirely sure why or how Tau is important and why its tangling causes such adverse effects. Therefore, researchers in Australia decided the super-resolution single molecule imaging technique to see how Tau and its mutants contribute to the damage of the brain. Scientists found that disorder of TAU affects the nanoclustering of the signalling protein Fyn.
The signalling protein Fyn moving and forming clusters in living brain cells – viewed using super-resolution microscopy. Image credit: University of Queensland
This interaction occurs in dendrites, where the communication between brain cells is happening. In short, Fyn forms aberrantly large clusters if Tau is mutated or tangled. This causes dysfunction of the synapse-junctions between nerve cells due to altered nerve signals.
Researchers say that in families with a very high risk of developing frontotemporal dementia over-cluster of Fyn is very common in the spines of dendrites. Professor Frédéric Meunier, one of the authors of the paper, said: “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. The spines of the dendrites are critical to how nerve cells communicate with each other and underpin memory and learning.”
We still don’t know the exact causes or mechanism of progression of Alzheimer’s disease. However, the signalling protein Fyn is linked to both the plaques of amyloid protein, which form between brain cells, and tangles of Tau protein. Understanding why these processes happen and how they are affecting the brain could lead to new treatment strategies. Treating dementia is going to be much more important in the near future.
World’s population is ageing and age-related dementia is going to be a bigger and bigger problem every year. We have to find reliable ways to treat it, but it is difficult without knowing exactly how it starts and develops. Hopefully, studies like this can fix this situation.
Source: University of Queensland