Rethinking Alzheimer's Disease

A recent report refers to
the increasing number of Alzheimer patient an "emergency."  Yet,
despite an enormous amount of research, and a handful of drugs, we are
not particularly close to having a robust intervention for this
condition.



Perhaps the reason is that we have been looking in the wrong
place.  Traditionally, brain disease tend to be thought of a
neuronal diseases, with many interventions aimed at neurotransmitters,
the chemical messengers that convey information from one neuron to
another.  But there is a lot more to the brain than neurons and
transmitters.



One researcher is going at this from a different angle.  href="http://faculty.bri.ucla.edu/institution/personnel?personnel_id=8435">George
Bartzokis, M.D., professor of psychiatry at UCLA, is looking at
myelin.  Myelin is a kind of covering for some neurons in the
brain.  It is produced by oligodendrocytes.  Oligodendrocytes
are a type of brain cell other than neurons. 



Prior studies have shown that the amount of myelin increases until
middle age, then starts to decrease.  Decreasing levels of myelin
are associated with decreasing speed of movement.  Past middle
age, people move more slowly.  That, by itself, is not the
problem.  Bartzokis' theory is that the problem comes from what
happens to the material that had been used to make the myelin.


href="http://www.newsroom.ucla.edu/portal/ucla/new-target-for-alzheimer-s-102065.aspx">Rethinking
Alzheimer's disease and its treatment targets


By Mark Wheeler

9/22/2009


...The myelin that is deposited in adulthood ensheaths
increasing numbers of axons with smaller axon diameters and so spreads
itself thinner and thinner, Bartzokis 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 faster than it can be
repaired.



The exclusive targeting of the amyloid-beta peptide for many
years is
understandable because the same genes and enzymes involved in
controlling myelination and myelin repair are, ironically, also
involved in the production of amyloid-beta proteins. Bartzokis' point
is that the amyloid beta may actually develop as a result of
the
natural process of the repair and maintenance of myelin...



We've known for a long time that neurons in the brains of persons with
Alzheimer Disease have abnormal deposits of protein: the infamous href="http://www.ahaf.org/alzheimers/about/understanding/plaques-and-tangles.html">amyloid
plaques and neurofibrillary tangles.  These structures were href="http://hod.kcms.msu.edu/timeline.php?y=1901-1906">described
by Alois Alzheimer about 100 years ago.  Bartzokis acknowledges
that they are important, but feels that they are late findings in the
development of the disease.  Rather that trying to figure out how
to get rid of them, he would like to figure out how to prevent them
from forming, or at least impede their development.


"For drug development then, the targets should be much
further upstream, earlier in the process before the AB plaques even
develop," he said.

 

Instead of focusing on reducing amyloid beta, Bartzokis argues, the
myelin model suggests entirely different approaches to treatment and
prevention of Alzheimer's disease that precede plaque formation.



Note that this hypothesis does not directly lead to any promising
intervention.  Rather, it suggests that much current drug
development is targeting the wrong things. 


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