Rich Club Brain Regions May Hold Clues to Huntington’s Disease

New research out of London has identified specific, highly connected brain regions, known as “rich club brain regions” that may be vulnerable in Huntington’s disease and possibly in other diseases in which there is progressive deterioration of brain cells (neurodegenerative diseases). The article, titled “Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington’s disease“ appeared September 17th in the journal Brain.

Huntington’s disease is a hereditary illness in which brain cells degenerate, causing involuntary, jerky movements known as chorea as well as dementia and psychiatric problems. It eventually leads to death. There is currently no cure and no effective treatments that can delay the disease.

Based on genetic information, and because Huntington’s runs in families, it is possible to predict Huntington’s disease years before symptoms appear. For this reason, it is a useful disease for understanding degenerative diseases of the nervous system in general. Loss of brain cell connections occur in regions that process movement, called the basal ganglia and cortex, early on in the disease.

According to the article, “The ‘rich club’ is a pattern of organization established in healthy human brains, where specific hub ‘rich club’ brain regions are more highly connected to each other than other brain regions.”

Led by Peter McColgan and Kiran Seunarine of the UCL Institutes of Neurology and Child Health, London, the investigators were interested in whether brain cells in this specific region are more vulnerable  in Huntington’s disease. The team used a technique known as “diffusion tractography and graph theoretical analysis” in 50 people with early Huntington’s disease, 38 people with Huntington’s disease and 47 healthy individuals who did not have Huntington’s disease.

They found that as suspected, rich club brain regions had a greater loss of brain cell connections in people with early Huntington’s or Huntington’s when compared with subjects who did not have the disease. According to the scientists “These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance.”

The research may help to explain why there is an extensive loss of connections in the brains of people with Huntington’s disease, and may also explain why people with this disease have severe problems with movement and cognition. In their article, the team wrote “These findings highlight the role of the rich club as a substrate for the structural connectivity loss seen in Huntington’s disease and have broader implications for understanding the connection between molecular and systems level pathology in neurodegenerative disease.”

Future targeted treatments, such as gene therapies or surgical interventions, may focus on rich club brain regions as treatments for Huntington’s as well as other neurodegenerative diseases.