Protein power: Dementia study reinforces role of damaging proteins in Alzheimer’s disease

A study, led by Professor Tara-Spires Jones at the University of Edinburgh, has elucidated the role of clusterin, a protein that accumulates at synapses in the brain, characteristic of Alzheimer’s disease.

Researchers studied brain tissue from deceased Alzheimer’s patients, which showed that the accumulation of clusterin occurs at synapses in addition to the aggregation of beta amyloid – a protein already known to be associated with the neurodegeneration found in patients with Alzheimer’s. 

However, in those not showing dementia symptoms, there was a noticeably lower level of these damaging proteins in the brain. It was therefore suggested that the accumulation of these proteins could contribute to the symptoms of dementia that arise as a consequence of Alzheimer’s disease.

The study also highlighted that individuals with the common risk gene, apolipoprotein E4 (ApoE4), had a greater degree of clusterin and amyloid beta aggregation at their synapses than those who had Alzheimer’s but not the risk gene. Researchers have hypothesised that a complex series of interactions between ApoE4, clusterin and amyloid beta occurs at synapses, leading to changes in the protein make-up of cells in the brain and its cellular activity. In conjunction, these could contribute significantly to the pathology of Alzheimer’s disease.

Previous research has shown that the loss of synapses in the brain can contribute significantly to the pathology of Alzheimer’s disease and its associated dementia symptoms. However, the role and importance of these damaging protein clumps remained unknown, as prior research had been limited by technology incapable of visualising synapses in detail. A single synapse is around 5000 times smaller than the thickness of a piece of paper and therefore, researchers took advantage of powerful technology (array tomography) available today to visualise detailed images of more than a million synapses in the brain. This provided an insight into the synaptic events that lead to Alzheimer’s disease.

Professor Spires-Jones, the Programme Leader at the UK Dementia Research Institute at the University of Edinburgh commented, “We have identified another player in the host of proteins that damage synapses in Alzheimer’s disease. Synapses are essential for thinking and memory, and preventing damage to them is a promising target to help prevent or reverse dementia symptoms.” Hence with studies such as this, researchers have highlighted the significance of protein aggregates at synapses in the brain and can continue to explore therapeutic targets for tackling Alzheimer’s disease and dementia.

Dementia describes a set of symptoms associated with damage to the brain, affecting memory, language and reasoning. Alzheimer’s disease is the most common form of dementia and currently has no cure, affecting around 500,000 people in the UK alone.The study was funded by the European Research Council and the UK Dementia Research Institute and can be found in the journal Brain Communications.

This post was written by Ebony Coward and edited by Tara Wagner-Gamble.