Last month, Dr. George Bartzokis, director of the UCLA Memory Disorders and Alzheimer's Disease Clinic, suggested in the journal Alzheimer's & Dementia that the breakdown of a type of myelin that develops late in life promotes the buildup of toxic amyloid plaques long associated with Alzheimer's disease.
Myelin is the insulation that wraps around nerve axons in the brain.
Now, in a new report currently online in the journal Neurochemical Research, Bartzokis turns his attention to Huntington's disease. Again, he suggests that a breakdown of myelin is the cause, but with a twist it is the myelin that develops early in the formation of the brain that breaks down prematurely and eventually leads to the disease's symptoms.
Huntington's disease (HD) is a rare, inherited neurological disorder that ultimately deprives individuals of their ability to control their movement, behavior and thinking. It affects approximately 30,000 people in the U.S., with another 150,000 at risk. While it is known that HD is caused by a mutation in a gene called Huntingtin (Htt), the exact mechanism by which the Htt gene causes or contributes to neuronal cell death and HD symptoms remains unclear. Bartzokis research suggests it is Htt's affect on myelin that may prove to be the cause.
The earliest parts of the developing brain include systems of neurons that control movement and behavior. These neurons have long axons finger-like projections that serve as the primary transmission lines of the nervous system covered with thick myelin sheaths. The sheaths are nourished by an ongoing supply of a protein called brain-derived neurotrophic factor, which travels down a neuron's axon.
Bartzokis believes the Htt gene interferes with this nourishment-delivery system, resulting in a breakdown of the myelin that depends on it. That, in turn, disrupts cell signaling, which results in the neuron's death.
The problem is compounded by the continual production of other cells that continue to make myelin. In HD, increasing numbers of these cells, called oligodendrocytes, are produced in an attempt to remyelinate axons whose myelin sheaths have broken down. This results in strikingly elevated numbers of oligodendrocytes years before the appearance of HD symptoms.