Researchers at the University of Auckland in New Zealand showed that the pattern of neuronal loss in three cortical brain areas in Huntington’s disease corresponds to the predominant symptom type in a patient.
The study, “Symptom heterogeneity in Huntington’s disease correlates with neuronal degeneration in the cerebral cortex,” published in the journal Neurobiology of Disease, contributes additional support for the notion that neurodegeneration in the cortex — the outermost layer of the brain — contributes to the development and symptoms of Huntington’s disease.
The research team had previously analyzed the brains of 14 deceased individuals with Huntington’s disease, comparing them to 13 people who died of non-neurological causes. They found that the pattern by which pyramidal cells die in eight regions of the cortex corresponded to the major symptom type of the patient: mainly movement, mainly mood, or mixed symptoms. Pyramidal neurons are the main cell type in the cortex sending stimulatory signals.
They also found that in some areas — responsible for movement, impulse control, and emotion — the loss of pyramidal cells was linked to loss of interneurons in the same area, which, in turn, corresponded to symptoms. Compared to pyramidal cells, interneurons are the main type of inhibitory neurons. The two types of nerve cells affect the signaling of one another, so it is not surprising that the death of one cell type is linked to the loss of the other type.
This time, researchers investigated three more brain areas using brains from the individuals used in the earlier study. The team focused on interneurons, and found that the loss of this cell type corresponded to the loss of pyramidal cells, documented earlier. Again, the loss of the two cell types correlated with symptoms.
Huntington’s disease was once considered primarily a disease affecting the brain’s basal ganglia — a deep brain structure dealing with movement coordination. Although it is generally accepted among researchers today that degeneration of nerve cells in the cortex contributes to the condition, the study helps researchers understand how a disease caused by mutations in a single gene can show so many different symptoms.