Public Release: 

MRI analysis shows brain connections that develop last decline first

Technology opens door for study of cause, treatment of Alzheimer's

University of California - Los Angeles

UCLA neuroscientists using a new MRI analysis technique to examine myelin sheaths that insulate the brain's wiring report that as people age, neural connections that develop last degenerate first. The computer-based analysis method is unique in its ability to examine specific brain structures in living people at millimeter resolution.

Published online by the Neurobiology of Aging earlier this year and scheduled to appear in the August 2004 print edition of the peer-reviewed journal, the study offers new insights into the role of myelin in brain aging and its contribution to the onset of Alzheimer's disease. In addition, the success of the MRI analysis technique opens new opportunities for studying the impact of lifestyle on brain aging and for developing medications that could slow aging or prevent Alzheimer's disease.

"The study increases our understanding of the role of myelin in brain development and degeneration, and demonstrates the usefulness of this MRI method for examining the single most powerful risk for Alzheimer's disease by far - age," said Dr. George Bartzokis, the study's lead investigator and visiting professor of neurology at the David Geffen School of Medicine at UCLA. He also is director of the UCLA Memory Disorders and Alzheimer's Disease Clinic and clinical core director of the UCLA Alzheimer's Disease Research Center.

Myelin is a sheet of lipid, or fat, with very high cholesterol content - the highest of any brain tissue. The high cholesterol content allows myelin to wrap tightly around axons, speeding messages through the brain by insulating these neural "wire" connections.

As the brain continues to develop in adulthood and as myelin is produced in greater and greater quantities, cholesterol levels in the brain grow and eventually promote the production of a toxic protein that together with other toxins attacks the brain. This toxic environment disrupts brain connections and eventually also leads to the brain/mind-destroying plaques and tangles visible years later in the cortex of Alzheimer's patients.

"The brain is not a computer, it is much more like the Internet," Bartzokis said. "The speed, quality and bandwidth of the connections determine its ability to process information, and all these depend in large part on the insulation that coats the brain's connecting wires.

"The results of our study show that in older age, the myelin insulation breaks down, resulting in a decline in the speed and efficiency of our Internet. Myelin and the cells that produce it are the most vulnerable component of our brain - the human brain's Achilles' heel," he said. "This safe, non-invasive technology can assess the development and degeneration of the brain's insulation in specific regions. Now that we can measure how brain aging proceeds in vulnerable regions, we can measure what treatments will slow aging down and thus begin in earnest to look at preventing Alzheimer's disease."

The UCLA research team examined the deterioration of myelin in the brain's splenium and genu regions of the corpus callosum, which connects the two sides of the brain. Neural connections important to vision develop early in life in the splenium, while connections important to decision making, memory, impulse control and other higher functions develop later in the genu.

The team found that the brain connections deteriorated three times as fast in the genu compared to the splenium. The study also notes that myelin deterioration is far greater throughout the brain of patients with Alzheimer's disease than in healthy older adults. The late myelinating regions are much more vulnerable and may be why the highest levels of reasoning and new memories are the first to go when one develops Alzheimer's disease, while movement and vision are unaffected until very late in the disease process.

These findings support the model of Alzheimer's as a disease driven by myelin breakdown. Bartzokis detailed this model in an article published in the January 2004 edition of the Neurobiology of Aging along with six independent commentaries and his response.

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The UCLA Department of Neurology encompasses 260 teachers, researchers and clinicians, and 245 staff personnel involved in more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks No. 1 among its peers nationwide in National Institutes of Health funding, with $23.4 million in active research grants.

The Alzheimer Disease Research Center at UCLA, directed by Dr. Jeffrey L. Cummings, was established in 1991 by a grant from the National Institute on Aging. Together with grants from the Alzheimer's Disease Research Center of California and the Sidell-Kagam Foundation, the center provides a mechanism for integrating, coordinating and supporting new and ongoing research by established investigators in Alzheimer's disease and aging. The Memory Disorders and Alzheimer's Disease Clinic of the center is an evaluation clinic for individuals over the age of 45 who are experiencing mild but gradually progressing cognitive or memory declines that are not related to other brain diseases such as strokes, tumors, infection, metabolic abnormalities, psychiatric disease or trauma.

Additional online resources:
David Geffen School of Medicine at UCLA: www.medsch.ucla.edu/
UCLA Department of Neurology: neurology.medsch.ucla.edu/
Alzheimer's Disease Research Center at UCLA: www.adc.ucla.edu/

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