Breakdown of myelin in brain implicated in Alzheimer’s
24 May 2007
New research suggests that it is the breakdown of so-called
late-stage myelin that promotes the build-up of toxic amyloid-beta fibrils
that eventually deposit in the brain and become the plaques which have long
been associated with Alzheimer’s disease.
Myelin is the fatty sheath that coats the axons of the nerves, allowing
for efficient conduction of nerve impulses. It is key to the fast processing
speeds that underlie our higher cognitive functioning.
Myelination continues sheathing 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 the April issue of the journal Alzheimer’s &
Dementia, Dr. George Bartzokis, UCLA professor of neurology, suggests
that it is the breakdown of this late-stage myelin that promotes the buildup
of toxic amyloid-beta fibrils that eventually deposit in the brain and
become the plaques which have long been associated with Alzheimer’s disease.
These amyloid products in turn destroy more and more myelin, according to
Bartzokis, disrupting brain signalling and leading to cell death and the
classic clinical signs of Alzheimer’s. If correct, the research suggests a
broader approach to therapeutic interventions for the disease.
And in a unique twist for modern-day science, Bartzokis tested his myelin
model of Alzheimer’s by comparing modern imaging results with maps of
cortical myelination that were published in the medical journal The
Lancet — back in 1901.
“Myelination is the single most unique aspect in which the human brain
differs from those of other species,” said Bartzokis, who also directs the
UCLA Memory Disorders and Alzheimer’s Disease Clinic. Myelin is produced by
oligodendrocytes, specialized glial cells that themselves become more
vulnerable with age.
“Myelination of the brain follows an inverted U-shaped trajectory,
growing strongly until middle age. Then it begins to breakdown,” Bartzokis
said. “Before the advent of modern medicine, very few persons lived beyond
age 50 and therefore, as a species, we evolved to continue myelinating over
our entire natural life span.”
As a result, the volume of myelinated white matter increases to a peak at
about age 50, then slowly begins to reverse and decline in volume as we
continue to age. The myelin that is deposited in adulthood ensheaths
increasing numbers of axons with smaller axon diameters, and so spreads
itself thinner and thinner, he said. As a result, it becomes more
susceptible to the ravages of age in the form of environmental and genetic
insults and slowly begins to break down.
“The myelin breakdown process mimics the developmental process of
myelination, but this time in reverse,” Bartzokis said. “That’s what we
think underlies the progressive spread of the neuritic plaques from the
late-myelinating regions toward the earlier-myelinating regions.”
Bartzokis noted that a similar progression has been described clinically
of the cognitive, functional and neurologic declines that accompany
Oligodendrocytes and myelin have the highest levels of iron of any brain
cells, Bartzokis said, and circumstantial evidence supports the possibility
that brain iron levels might be a risk factor for age-related
neurodegenerative diseases like Alzheimer’s. In the study, he suggests that
myelin breakdown in the late-myelinating regions releases iron, which
promotes the development of the toxic amyloid oligomers and plaques, which
in turn destroy more myelin.
Bartzokis tested his hypothesis by examining published images of amyloid
deposition acquired in living individuals; the images were made using
radiolabeled ligands, molecules that bind to amyloid plaques in the brains
of Alzheimer’s patients. Next, he compared the physical location of these
plaques to much earlier work published in a 1901 edition of The Lancet that
mapped the locations in the brain where late-stage myelination occurs. The
two matched up perfectly.
“It was pretty striking,” Bartzokis said. “And the results are easily
testable using currently available imaging methods. What’s important is that
these results have implications for novel therapeutic interventions that
could target oligodendrocytes, myelin and iron deposits in the brain.”
Post this page to Del.icio.us