Immune Cells In Gut Help Spread Parkinsons Disease To Brain: Study

A new study demonstrates how immune cells in the gut facilitate the spread of Parkinson's disease to the brain, pointing towards a potential target for therapy. Parkinson's disease -- a neurodegenerative condition characterised by tremors, stiffness, and slowness of movement, among others -- is thought to originate in the gut, as one of the first cranial regions to be affected is the dorsal motor nucleus of the vagus nerve which is directly connected to the gut. However, researchers from University College London said the exact neurological pathways of the spread of Parkinson's disease to the brain were not known earlier.

The study, conducted in mice and published in the Nature journal, identifies a key role of gut macrophages -- a specialised immune cell that kills pathogens -- in the transfer of toxic proteins from the gut to the brain.

Reducing the number of gut macrophages led to reduced spread of such proteins, and improved motor symptoms in mice with Parkinson's disease, the researchers said.

Co-lead author Tim Bartels, group leader at the UK Dementia Research Institute at University College London, said, neurodegenerative diseases have slow trajectories over decades.

"Understanding how Parkinson's begins in the body could allow us to develop simple blood tests to screen for it, enabling diagnosis long before damage to the brain starts. Having the ability to detect and manage Parkinson's before it even reaches the brain could have a huge impact for those affected," Bartels said.

Studies have shown how people with Parkinson's disease exhibit gut symptoms long before motor symptoms begin -- for example, chronic constipation decades before diagnosis.

The researchers isolated a specific neurotransmitter alpha-synuclein (an amino acid) from brains of people who have died due to Parkinson's disease.

Tiny amounts of the patient-derived alpha-synuclein were inserted into the small intestines of mice and the spread of the toxic proteins from the gut to the brain was tracked.

According to researchers, gut macrophages or immune cells consumed the alpha-synuclein protein, and began showing signs of dysfunction in their lysosomal systems, which is responsible for breaking down the cell's waste material.

The team found that the macrophages then signalled T-cells -- part of the body's immune response -- to travel from the gut to the brain.

Depleting the number of gut macrophages before injecting alpha-synuclein into the small intestine of mice was found to result in reduced levels of the toxic proteins in the brain.

The result suggests a possible therapeutic strategy -- targeting the immune cells and preventing them from reaching the brain, researchers said.

Co-lead author Dr Soyon Hong, group leader at the UK Dementia Research Institute, said, "Our study shows that immune cells are not bystanders in Parkinson's; these gut macrophages are responding, albeit in a dysfunctional way." "This presents an opportunity to think about how we can boost the function of the immune system and these cells, so that they respond in the correct manner and help to slow or stop the spread of disease," Hong said. 

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