New research: a map of molecular brain changes during ageing

diagram representing coloured molecules in various shapes

May 2019: Our researchers have generated a 'map' of how protein molecules change in the brain during normal ageing, which can be used as a benchmark to investigate neurodegeneration.

As we all know, our brains deteriorate during normal healthy ageing. We might not be able to think or react as fast as we could when we were younger, and our memory might not be quite as sharp.

If you zoom in on the brain cells to investigate what is causing these changes, one of the differences you would see is a loss of 'spines' on the nerve cells (neurons), and a loss of the connections between neurons, which are called synapses. This loss means that the brain cells can't connect with each other, and transmit information, quite as well as they previously could.

In our latest research, our investigators have zoomed in still further, to examine the changes in the protein molecules that happen in neurons during ageing. An understanding of normal healthy ageing is a really important benchmark so that researchers can test for differences between normal healthy ageing and neurodegenerative conditions such as MND, Alzheimer's and Parkinson's. By understanding which molecular changes are normal, and which lead to neurodegenerative conditions, researchers can work out which ones are the best to target with drugs.

A collaborative team led by Dr Tom Wishart, and involving other Euan MacDonald Centre researchers Prof Tom Gillingwater, Dr Paul Skehel and Prof Colin Smith plus international collaborators, examined brain tissue from both humans and rhesus macaques (a species of monkey). All the brain tissue was derived from 'brain bank' samples that were already archived for research: the human tissue was from the MRC Edinburgh Brain and Tissue Bank and the macaque tissue was from the Oregon National Primate Research Center.

The researchers examined brain tissue at three different ages (young, middle-aged, and old) and also from two different brain regions - one where the synapses are known to be particularly vulnerable to degeneration during ageing, and one where they are resistant. They compared thousands of proteins according to how commonly they were present in each sample.

Interestingly, the processes of normal healthy ageing were found to be very similar between humans and macaques. The researchers identified proteins that change during healthy ageing, and importantly, identified differences between brain regions.

The researchers have generated a data resource for the research community, identified proteins that might be involved in the ageing of synapses, and which ones might make particular brain regions particularly susceptible to degeneration in conditions like MND. 

These findings are an excellent springboard for further research and understanding about the human brain and neurodegenerative conditions like MND.

Related links

Read the scientific article in Cell Reports: Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

MRC Edinburgh Brain and Tissue Bank

Researcher profile: Dr Tom Wishart

This article was published on: Wednesday, May 01, 2019