Institute of Genetics and Cancer

New publication: Uncovering molecular signatures of brain health

Researchers from the Institute of Genetics and Cancer map relationships between epigenetics, protein biology and brain health.

Image of a brain
Photo by Milad Fakurian on Unsplash

The interplay between environment, biology and brain health is important to understand in the context of the ageing brain. 

Unlike the genetic information that is stored in our DNA, our epigenetic signature is dynamic throughout our lives. Epigenetic modifications to DNA can record the body’s response to a range of environmental and lifestyle stressors and have been associated with the risk of developing neurological diseases. Protein markers from the blood have also been shown to associate with epigenetic modifications and are often associated with neurological diseases.

Here, in a study recently published in Nature Communications, Danni Gadd, Riccardo Marioni and colleagues wanted to understand whether there were protein markers of brain health that had epigenetic signatures. 

They identified 191 of a possible 4,235 proteins from the blood that were related to brain health in 1,065 individuals from the Generation Scotland cohort. They looked at brain imaging measures like global grey matter volume, cognitive tests such as logical memory and APOE status – which is a known genetic risk factor for dementia.

They also mapped relationships between each of the 4,235 blood proteins available in the study and epigenetic modifications across DNA. They did this in a subset of 774 individuals by measuring DNA methylation – a type of epigenetic modification. 

By overlapping their findings, the authors were able to pinpoint protein markers of brain health that also had epigenetic signatures. 

One example of interest is DNA methylation in the SLC7A11 gene. DNA methylation at this gene was associated with three protein markers of either increased relative brain age, or reduced cognitive processing speed – both indicators of poorer brain health. The specific DNA methylation site the authors identified (cg06690548) has been linked to Parkinson’s Disease and Motor Neuron Disease risk in previous epigenetic studies. Markers such as these could therefore be explored in future to understand whether they can be targeted to improve brain health.

Taken together, the results deepen our understanding of the possible molecular regulators of brain health. A video describing the study can be viewed at the link below.

Danni Gadd is a PhD student on the Wellcome Trust Translational Neuroscience programme.

Links

Manuscript (external) 

YouTube video (external) 

Marioni Group website 

Marioni group Twitter (external)

Danni Gadd profile 

Danni Gadd Twitter (external) 

Summary statistics for the methylation studies of 4,231 protein levels (external)