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David Geffen School of Medicine
The Cutting Edge

Rethinking Alzheimer's Disease

Adopting the myelin model could enable
clinicians to track changes in the brain
and intercede before signs of Alzheimer's
disease are evident.

THE STANDARD hypothesis for what causes Alzheimer’s disease is that toxic protein fragments known as amyloid beta deposit in the brain as sticky plaques, resulting in the disease. Billions of dollars is spent targeting amyloids – but what if it is the wrong target? What if the disease begins much earlier, fueled by a natural process?

Reporting in the journal Neurobiology of Aging, George Bartzokis, M.D., professor of psychiatry and a member of UCLA’s Brain Research Institute, argues that a better working hypothesis is the “myelin model.” “Th e greatest promise of the myelin model of the human brain is its application to the development of new therapeutic approaches,” Dr. Bartzokis says.

Like insulation around wires, myelin is a fatty sheath that coats our nerve axons, allowing for efficient conduction of nerve impulses. But the lifelong, extensive myelination of the human brain also makes it uniquely vulnerable to damage. The central premise of the myelin model is that it is the normal, routine maintenance and repair of myelin throughout life that ultimately initiates the mechanisms that produce degenerative diseases like Alzheimer’s. Dr. Bartzokis notes that myelination of the brain follows an inverted U-shaped trajectory, growing strong until our 50s, when it very slowly begins to unravel as we age – eventually breaking down faster than it can be repaired.

Most drugs currently being developed for Alzheimer’s are targeting amyloid beta, but little if any clinical improvement is being seen. This process is, according to Dr. Bartzokis, “similar to cleaning up a house that’s been flooded by water but never repairing the actual pipe that created the flood.”

The myelin model suggests entirely different approaches to treatment and prevention of Alzheimer’s disease that precede plaque formation. With modern brain imaging technology, clinicians could track the dynamic changes taking place in the brain and intercede well before any signs of Alzheimer’s are seen.
“With earlier intervention,” Dr. Bartzokis says, “we could reduce and potentially eliminate the increasingly catastrophic burden of dementia on the individual and their family, the healthcare system and our society.”


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