How fast is your brain ageing? Proteins in blood offer clues

Researchers have identified 13 proteins in the blood that predict how quickly or slowly a person’s brain ages compared with the rest of their body.

Their study¹, published in Nature Aging on 9 December, used a machine-learning model to estimate ‘brain ages’ from scans of more than 10,000 people. The authors then analysed thousands of scans alongside blood samples and found eight proteins that were associated with fast brain ageing, and five linked to slower brain ageing.

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“Previous studies mainly focused on the association between the proteins and the chronological age, that means the real age of the individual,” says study co-author Wei-Shi Liu, a neurologist at Fudan University in Shanghai, China.

However, studying biomarkers linked to a person’s brain age could help scientists to identify molecules to target in future treatments for age-related brain diseases. “These proteins are all promising therapeutic targets for brain disorders, but it may take a long time to validate them,” says Liu.

Brain age gap

Using machine learning to analyse brain-imaging data from 10,949 people, Liu and his colleagues created a model to calculate a person’s brain age, using hundreds of structural features such as the overall brain volume, thickness of the cortex and amount of white matter. The difference between the brain age and the chronological age, known as the brain age gap, can help to indicate brain health.

On average, the brain ages of participants differed from their chronological ages by around three years either way — meaning that most people had a brain that was biologically slightly ‘younger’ or ‘older’ than they were.

The researchers wanted to identify proteins that are associated with large brain age gaps, so they analysed the levels of 2,922 proteins in blood samples from 4,696 people, more than half of whom were female, and compared them with the same people’s brain ages according to their brain scans. They identified 13 proteins that seemed to be connected with large brain age gaps, some of which are known to be involved in movement, cognition and mental health.

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One key protein was brevican (BCAN), which helps to form and maintain the network of molecules around cells and is involved in learning and memory. Higher levels of BCAN were associated with slower brain ageing. Brain cells in people with Alzheimer’s disease also express less BCAN than do those in healthy people.