A study within the UK DRI at Edinburgh into Motor Neurone Disease (MND) has shown that a loss of synapses in the brain is linked to cognitive decline.
MND is a rapidly progressing terminal illness which can cause someone to lose the ability to walk, talk, eat, drink or breathe unaided. It is caused by the breakdown of motor neurons – the cells in the brain and spinal cord in charge of muscle control.
These cells are connected together by synapses, which were the primary focus of the study.
It discovered that the loss of synapses is associated with a decline in cognitive brain function, including thinking, planning, reasoning and emotions, which is seen in up to 50% of patients with Amyotrophic Lateral Sclerosis (ALS) - the most common type of MND.
The discovery was made with extremely powerful technology, used in MND for the first time, which allowed the scientists to view detailed images of synapses around 5000x smaller than the thickness of a sheet of paper.
The study was led by Dr Chris Henstridge, in the laboratory group of UK DRI Professor Tara Spires-Jones.
Dr Henstridge believes the results could open up an entire new field of synapse-focused MND research. The link was made after comparing data from people with MND who may have experienced some changes in their behaviour or ability to reason and make decisions. This data was then compared against those who have MND but who do not experience any of these changes, and against people who do not have the disease.
The discovery mirrors similar findings in Alzheimer’s disease, which have since inspired a new area of research into the role synapses play in cognitive change in neurodegenerative diseases.
Dr Henstridge said: “Up to 50% of ALS patients have some kind of change in brain function as well as motor problems. For a long time, researchers have tried to uncover the mechanism that might be driving this change in brain function, but have struggled. For the first time, we have discovered that a breakdown in connections between neurons in the brain is associated with a decline in brain function in ALS. Interestingly, synapse loss is a common feature of many neurodegenerative diseases in which a decline in brain function occurs, such as Alzheimer’s disease.”
“When synapse loss was first correlated with cognitive decline in Alzheimer’s disease, it kick started a huge field of synapse-focused research which has led to significant advancements in our understanding of the disease and even resulted in clinical trials of synapse-targeted therapeutics. My hope is that our new findings will initiate a similar wave of important research and ultimately lead to novel therapies for MND.”
UK DRI Professor Tara Spires-Jones, senior author on the paper, said: "In this study, we observed that loss of synapses - connections between brain cells - is associated with declining cognitive function in people with ALS. Further, we saw accumulation of the toxic protein TDP43 inside individual synapses, providing a potential target for future drug treatments. Removing this toxic protein from the synapses could benefit patients. These discoveries are similar to our recent work in Alzheimer's disease and Dementia with Lewy Bodies indicating that toxic protein accumulation contributes to synapse loss and dementia in several diseases. "
This study based within UK DRI at Edinburgh received funding from MND Scotland and is published in journal Acta Neuropathologica.
