A novel study by researchers at Oxford Population Health reveals previously unknown protein links to neurodegenerative diseases, including eight proteins associated with Alzheimer’s disease.
Neurodegenerative diseases are a group of brain diseases, characterised by progressive loss of nerve cells and other changes in the brain. Alzheimer’s and Parkinson’s are the most common among the neurodegenerative diseases.
Researchers from Oxford Population Health investigated how protein levels in the blood are related to these neurodegenerative diseases, as well as multiple sclerosis, a disease where the immune system attacks the nerve cells, and amyotrophic lateral sclerosis, a relatively rare but fatal disease that is caused by the progressive loss of nerve cells in the brain and spinal cord.
Dr Lazaros Belbasis, lead author and British Heart Foundation Centre of Research Excellence Intermediate Transition Research Fellow at Oxford Population Health, said ‘Proteins play a key role in a range of biological processes, including the development of neurodegenerative diseases. Our study aims to help combat the global burden of these diseases by identifying their underlying mechanisms and potential drug targets.’
The researchers used genetic data from the UK Biobank and the deCODE Health Study to analyse more than 2,700 blood proteins measured through two different technologies, and to study their association with these neurodegenerative diseases. The results are published in Brain.
They identified 50 proteins that were strongly associated with neurodegenerative diseases. Almost half of them (23 of the 50 protein-disease associations) were previously unknown.
The researchers identified novel links between eight proteins and Alzheimer's disease. These newly-associated proteins are linked to the complement system, which is part of the body’s immune response, as well as microglia, which are immune cells in the brain, and lysosomes, which break down waste materials in cells.
The study identified new associations with multiple sclerosis for proteins linked to immune response, the brain’s protective blood-brain barrier, the functions of oligodendrocytes that insulate nerve fibres, and processes involving the node of Ranvier and dorsal root ganglion, which are essential for speeding up nerve signal transmission.
For Parkinson’s disease, a newly-associated link to the interleukin-6 pathway, which plays a role in inflammation and immune response, was identified. Amyotrophic lateral sclerosis was linked to lysosomes that cleans up cells, the brain's protective barrier, and astrocytes, which are support cells for neurons.
The study also explored how these proteins might affect various brain imaging traits, providing further insights into the relationship between protein levels and brain changes in neurodegenerative diseases.
Associate Professor Robin Walters, senior author and Senior Scientist at Oxford Population Health, said ‘This study reveals previously unknown links between particular proteins and the risk of neurodegenerative diseases. These proteins are likely to be important for brain health and to play a key role in the mechanisms leading to diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and multiple sclerosis. We hope that our results will inform future development of treatments for these devastating diseases.’
The study highlights the potential of using genetic and protein data to uncover disease mechanisms and identify potential new drug targets. While the researchers only examined a small portion of proteins in the blood, expanding the protein testing methods and studying different protein forms could provide deeper insights into how proteins influence neurodegenerative diseases.