New research findings: Synapse loss may underlie brain changes in MND

New findings from Euan MacDonald Centre researchers provide insight into the pathways that underlie the changes in thinking and behaviour experienced by some people with MND.

Dr Chris Henstridge, Professor Tara Spires-Jones and colleagues have used extremely powerful imaging technology to compare the junctions between neurons – called synapses – in people with and without MND.

Importantly, the people with MND were split into two groups: those who have experienced changes in their behaviour or thinking, and those who have not. Approximately 50% of people with MND experience these so-called cognitive changes.

The technology used is so powerful that the scientists can view detailed images of the synapses, which are around 5000x smaller than the thickness of a sheet of paper. It is the first time this technology has been used on samples from people with MND.

Dr Henstridge discovered that a loss of synapses, resulting in a breakdown of connections in the brain, is associated with a decline in brain function, including thinking, planning, reasoning and emotions.

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.”

The work was funded by MND Scotland. It was made possible by the Scottish national MND Register. The Register compiles accurate statistics on people with MND in Scotland and gives MND patients across Scotland the opportunity to donate their DNA for research purposes.

Related links

Read the scientific paper in Acta Neuropathologica: Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis, by Henstridge et al. doi.org/10.1007/s00401-017-1797-4

Find out more about the MND Register on the CARE-MND website

Professor Tara Spires-Jones Principal Investigator profile