Imaging study links key genetic risk for Alzheimer's disease to myelin breakdown

A new UCLA imaging study shows that age-related breakdown of myelin, the fatty insulation coating the brain's internal wiring, correlates strongly with the presence of a key genetic risk factor for Alzheimer disease.

The findings are detailed in the January edition of the peer-reviewed journal Archives of General Psychiatry and add to a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life.

In addition, the study demonstrates how genetic testing coupled with non-invasive evaluation of myelin breakdown through magnetic resonance imaging (MRI) may prove useful in assessing treatments for preventing the disease.

"Myelination, a process uniquely built up in humans, arguably is the most important and most vulnerable process of brain development as we mature and age. These new findings offer, for the first time, compelling genetic evidence that myelin breakdown underlies both the advanced age and the principal genetic risks for Alzheimer disease," said Dr. George Bartzokis, professor of neurology at UCLA's David Geffen School of Medicine.

"The human brain functions as a high-speed Internet system," said Bartzokis, director of the UCLA Memory Disorders and Alzheimer Disease Clinic and Clinical Core director of the UCLA Alzheimer Disease Research Center. "The quality of the brain's connections is key to its speed, bandwidth, fidelity and overall on-line capability."

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 increase and eventually promote the production of a toxic protein that attacks the brain. The protein attacks myelin, disrupts message transfer through the axons and eventually can lead to the brain/mind-destroying plaques and tangles visible years later in the cortex of Alzheimer patients.

The Apolipoprotein E (ApoE) genotype is the second most influential Alzheimer risk factor, after only advanced age. The study used MRI to assess myelin breakdown in 104 healthy individuals between ages 55 and 75 and determine whether the shift in the age at onset of Alzheimer disease caused by the ApoE genotype is associated with age-related myelin breakdown.

The results show that in later-myelinating regions of the brain, the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.

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Funding for the research was provided by grants from the National Institute of Mental Health, the National Institute on Aging, the California Department of Health Services, the Sidell Kagan Foundation and the Department of Veterans Affairs.

Other UCLA neuroscientists involved in the study included Po H. Lu, Dr. Daniel H. Geschwind, Nancy Edwards, Jim Mintz and Dr. Jeffrey L. Cummings.

The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks No. 2 among its peers nationwide in National Institutes of Health funding.

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 Kagan Foundation, the center provides a mechanism for integrating, coordinating and supporting new and ongoing research by established investigators in Alzheimer disease and aging. The Memory Disorders and Alzheimer's Disease Clinic of the Alzheimer Disease Research 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.

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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