Science + Technology

Breakdown of Myelin Implicated in Alzheimer’s, UCLA Research Shows

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Wisdom comes with age(doesn't it?), but not without a process that takes place in the brain calledmyelination. Myelin is the fatty sheath that coats the axons of the nerves,allowing for efficient conduction of nerve impulses. It is key to the fastprocessing speeds that underlie our higher cognitive functioning, including,yes, wisdom.

Myelination continuessheathing axons until we reach the age of about 50, but in these later stages,the myelin becomes more and more susceptible to damage. Now, in a report in theApril issue of the journal Alzheimer's & Dementia,Dr. George Bartzokis, UCLA professor of neurology, suggests that it isthe breakdown of this late-stage myelin that promotes the buildup of toxicamyloid-beta fibrils that eventually deposit in the brain and become theplaques which have long been associated with Alzheimer's disease.

These amyloid products inturn destroy more and more myelin, according to Bartzokis, disrupting brainsignaling and leading to cell death and the classic clinical signs ofAlzheimer's. If correct, the research suggests a broader approach totherapeutic interventions for the disease.

And in a unique twist formodern-day science, Bartzokis tested his myelin model of Alzheimer's bycomparing modern imaging results with maps of cortical myelination that werepublished in the medical journal The Lancet — back in 1901.

"Myelination is the single mostunique aspect in which the human brain differs from those of other species,"said Bartzokis, who also directs the UCLA Memory Disorders and Alzheimer'sDisease Clinic. Myelin is produced byoligodendrocytes, specialized glial cells that themselves become morevulnerable with age.

"Myelination of the brainfollows an inverted U-shaped trajectory, growing strongly until middle age.Then it begins to breakdown," Bartzokis said. "Before the advent of modernmedicine, very few persons lived beyond age 50 and therefore, as a species, weevolved to continue myelinating over our entire natural life span."


As a result, the volume of myelinatedwhite matter increases to a peak at about age 50, then slowly begins to reverseand decline in volume as we continue to age. The myelin that is deposited inadulthood ensheaths increasing numbers of axons with smaller axon diameters,and so spreads itself thinner and thinner, he said. As a result, it becomes moresusceptible to the ravages of age in the form of environmental and genetic insultsand slowly begins to break down.

"The myelin breakdown processmimics the developmental process of myelination, but this time in reverse," Bartzokissaid. "That's what we think underlies the progressive spread of the neuriticplaques from the late-myelinating regions toward the earlier-myelinatingregions."

Bartzokis noted that asimilar progression has been described clinically of the cognitive, functionaland neurologic declines that accompany Alzheimer's disease.

Oligodendrocytes and myelinhave the highest levels of iron of any brain cells, Bartzokis said, andcircumstantial evidence supports the possibility that brain iron levels mightbe a risk factor for age-related neurodegenerative diseases like Alzheimer's. Inthe study, he suggests that myelin breakdown in the late-myelinating regionsreleases iron, which promotes the development of the toxic amyloid oligomersand plaques, which in turn destroy more myelin.

Bartzokis tested hishypothesis by examining published images of amyloid deposition acquired inliving individuals; the images were made using radiolabeled ligands, moleculesthat bind to amyloid plaques in the brains of Alzheimer's patients. Next, hecompared the physical location of these plaques to much earlier work publishedin a 1901 edition of The Lancet that mapped the locations in the brain wherelate-stage myelination occurs. The two matched up perfectly.

"It was pretty striking,"Bartzokis said. "And the results are easily testable using currently availableimaging methods. What's important is that these results have implications fornovel therapeutic interventions that could target oligodendrocytes, myelin andiron deposits in the brain."

The research was funded bythe National Institute of Mental Health, the National Institute on Aging, andthe Psychiatry Services of the Department of Veterans Affairs. Po Lu, anassistant clinical professor in the UCLA Department of Neurology, and Jim Mintz,professor of psychiatry at the David Geffen School of Medicine at UCLA, wereco-authors on the study.

The UCLA Department ofNeurology encompasses 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 muscledisorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headachesand migraines, neurorehabilitation, and neurovascular disorders. The departmentranked No. 1 among its peers nationwide in National Institutes of Healthfunding in 2005. For more information, visit http://neurology.medsch.ucla.edu.

-UCLA-

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