On 10/13/2013 09:37 PM, Mark Thorson wrote:
Mark,
There is no indication that the makeup of beta amyloid had any mutation
at all in that Nature study. The mutation was in the amyloid precursor
protein, and the reduction in beta amyloid is presumably due to the a
change in the 3-dimensional conformation of the precursor protein which
made it more difficult for beta and gamma secretase to break it into
beta amyloid.
However, all of this is pretty much irrelevant to the goal of defeating
Alzheimer's. Researchers use transgenic mice with a multiple mutationa
which raises beta amyloid levels so much that the mice develop
Alzheimer's like symptoms within one year, instead of the decades it
takes in humans. In theory, if a drug or treatment has been found to
work in these animals, then human trials can follow.
In practice, researchers have already found a way not just to prevent
male transgenic mice from developing Alzheimer's symptoms, but to make
these mice smarter than normal mice. In fact, these mice never even
experienced the degradation in memory that is normally associated with
aging. See: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506430
The "treatment" used was to knock out the gene that produces the enzyme
aromatase. As a result, these mice had higher than normal levels of
testosterone, with none of the testosterone being converted to estrogen.
Of course there is no way to introduce such a mutation in men. However,
adding sufficient testosterone and using aromatase inhibitors should
come close to emulating the results of this mutation. However, even
though this article was published in 2010, I can find no evidence that
any doctor has tried this treatment on men. Basically, men who have the
beginning symptoms of Alzheimer's currently go to their doctors and are
told about expensive drugs that masks some of their symptoms for a few
months. Nobody is even told about the possiblity of testosterone plus
aromatase inhibitor being a cure or even more than a cure.
My question is why are doctors behaving this way? Are they ignorant of
the 2010 study? Are they afraid to use a drug and hormone off label to
save their patient's life when that patient is otherwise doomed to a
horrible certain death? Are they just waiting for somebody else to do a
clinical trial before they dare try this treatment? I am sincerely
puzzled, since I know of no doctors who treat Alzheimer's and therefore
have no way of getting the answer to these questions.
Ed Friedman
Post by Mark ThorsonPost by Mark ThorsonPost by Ed FriedmanIt is a fact that beta amyloid is heavily involved in causing
Alzheimer's. This was proven beyond a shadow of a doubt when the Nature
article was published in 2012 showing that a single mutation which
reduced beta amyloid production by approximately 40% greatly reduced the
incidence of Alzheimer's. If beta amyloid was in fact protective, then
this mutation should have resulted in more Alzheimer's, not less. Some
beta amyloid is essential for normal brain functioning, but too much
causes Alzheimer's.
Do you have a link to this Nature article?
There are many studies cited as putative evidence
for this or that which proves to be nothing of the
kind when looked at.
I found it. It's the same Icelandic study you've
brought up before.
http://extremelongevity.net/wp-content/uploads/app.pdf
I'll comment more specifically on this study later,
but it does not prove (or even suggest) that amyloid
beta _causes_ AD. Nobody denies that amyloid beta
plays some important role, good or bad, in the late-
stage pathology of AD. This study only examined people
age 80 or older, so it was not concerned with any early
events in AD. It certainly does not implicate amyloid
beta in any early causal events of AD.
It's like forest fires. Douglas fir forests are denser
and burn more intensely than oak forests. But that
doesn't mean Douglas fir is the _cause_ of forest fires.
Lightning strikes, lit cigarette butts thrown from cars,
and burning embers from campfires cause forest fires.
But Douglas fir certainly affects how bad a forest fire
will be.
I don't believe amyloid beta is protective against AD,
but if it were, the mutation in this study could make
a form of amyloid beta with enhanced activity against
whatever it is that causes AD. That would be entirely
consistent with the results reported in the study.