Study identifies pathology of Huntington's disease

October 17, 2012

A study led by researchers at Boston University School of Medicine (BUSM) provides novel insight into the impact that Huntington's disease has on the brain. The findings, published online in Neurology, pinpoint areas of the brain most affected by the disease and opens the door to examine why some people experience milder forms of the disease than others.

Richard Myers, PhD, professor of neurology at BUSM, is the study's lead/corresponding author. This study, which is the largest to date of brains specific to Huntington's disease, is the product of nearly 30 years of collaboration between the lead investigators at BUSM and their colleagues at the McLean Resource Center, Massachusetts General Hospital and Columbia University.

Huntington's disease (HD) is an inherited and fatal that typically is diagnosed when a person is approximately 40 years old. The gene responsible for the disease was identified in 1993, but the reason why certain neurons or die remains unknown.

The investigators examined 664 autopsy samples with HD that were donated to the McLean Brain Bank. They evaluated and scored more than 50 areas of the brain for the effects of HD on neurons and other brain cell types. This information was combined with a genetic study to characterize variations in the Huntington gene. They also gathered the clinical neurological information on the patients' age when HD symptoms presented and how long the patient survived with the disease.

Based on this analysis, the investigators discovered that HD primarily damages the brain in two areas. The , which is located deep within the brain and is involved in motor control and involuntary movement, was the area most severely impacted by HD. The outer cortical regions, which are involved in cognitive function and thought processing, also showed damage from HD, but it was less severe than in the striatum.

The investigators identified extraordinary variation in the extent of cell death in different brain regions. For example, some individuals had extremely severe outer cortical degeneration while others appeared virtually normal. Also, the extent of involvement for these two regions was remarkably unrelated, where some people demonstrated heavy involvement in the striatum but very little involvement in the cortex, and vice versa.

"There are tremendous differences in how people with Huntington's disease are affected," Myers said. "Some people with the disease have more difficulty with motor control than with their cognitive function while others suffer more from cognitive disability than issues."

When studying these differences, the investigators noted that the cell death in the striatum is heavily driven by the effects of variations in the Huntington gene itself, while effects on the cortex were minimally affected by the HD gene and are thus likely to be a consequence of other unidentified causes. Importantly, the study showed that some people with HD experienced remarkably less neuronal cell death than others.

"While there is just one genetic defect that causes Huntington's disease, the disease affects different parts of the brain in very different ways in different people," said Myers. "For the first time, we can measure these differences with a very fine level of detail and hopefully identify what is preventing brain in some individuals with HD."

The investigators have initiated extensive studies into what genes and other factors are associated with the protection of neurons in HD, and they hope these protective factors will point to possible novel treatments.

Explore further: Reach2HD, a Phase II study in Huntington's disease, launched

Related Stories

Reach2HD, a Phase II study in Huntington's disease, launched

June 7, 2012
The Huntington Study Group (HSG), under the leadership of Ray Dorsey, M.D. with Johns Hopkins Medical and Diana Rosas, M.D. with Massachusetts General Hospital, is conducting a clinical trial in Huntington's disease (HD) ...

Striatal brain volume predicts Huntington disease onset

April 26, 2012
Huntington disease (HD) is an inherited neurodegenerative disorder caused by a defect on chromosome four where, within the Huntingtin gene, a CAG repeat occurs too many times. Most individuals begin experiencing symptoms ...

Dantrolene protects neurons from Huntington's disease

November 25, 2011
Huntington's disease (HD) is characterized by ongoing destruction of specific neurons within the brain. It affects a person's ability to walk, talk, and think - leading to involuntary movement and loss of muscle co-ordination. ...

Recommended for you

Neurons involved in learning, memory preservation less stable, more flexible than once thought

August 17, 2017
The human brain has a region of cells responsible for linking sensory cues to actions and behaviors and cataloging the link as a memory. Cells that form these links have been deemed highly stable and fixed.

Researchers make surprising discovery about how neurons talk to each other

August 17, 2017
Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge ...

Researchers show how particular fear memories can be erased

August 17, 2017
Researchers at the University of California, Riverside have devised a method to selectively erase particular fear memories by weakening the connections between the nerve cells (neurons) involved in forming these memories.

How we recall the past: Neuroscientists discover a brain circuit dedicated to retrieving memories

August 17, 2017
When we have a new experience, the memory of that event is stored in a neural circuit that connects several parts of the hippocampus and other brain structures. Each cluster of neurons may store different aspects of the memory, ...

Scientists identify central neural circuit for itch sensation

August 17, 2017
Itching is an unpleasant sensation associated with the desire to scratch, and the itch sensation is an important protective mechanism for animals. However, chronic itch, often seen in patients with skin and liver diseases, ...

Study uncovers specialized mouse neurons that play a unique role in pain

August 17, 2017
Researchers from the National Institutes of Health have identified a class of sensory neurons (nerve cells that electrically send and receive messages between the body and brain) that can be activated by stimuli as precise ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.