[ExI] Fwd: Alzheimer's vaccine trial a success

Rafal Smigrodzki rafal.smigrodzki at gmail.com
Thu Jul 26 21:47:30 UTC 2012

---------- Forwarded message ----------
From: Rafal Smigrodzki <rafal.smigrodzki at gmail.com>
Date: Thu, Jul 26, 2012 at 5:47 PM
Subject: Re: [ExI] Alzheimer's vaccine trial a success
To: John Clark <johnkclark at gmail.com>

On Thu, Jul 26, 2012 at 3:51 PM, John Clark <johnkclark at gmail.com> wrote:
> On Thu, Jul 26, 2012 at 2:36 PM, Rafal Smigrodzki
> <rafal.smigrodzki at gmail.com> wrote:
>> > Amyloid is not the cause of AD. Repeat, then repeat again,
> Maybe, maybe not, but they are certainly closely linked; just a few days ago
> it was reported that people with a rare mutation in the gene that codes for
> the  amyloid-beta precursor protein are much more unlikely than the general
> population to get Alzheimer's disease. And in general those lucky enough to
> have this mutation have better mental function when they are between 80 and
> 100 than those who don't.

### Yes, we have known for something like 20 years that APP mutations
can cause familial AD (FAD) but there was no linkage between APP gene
and SAD (sporadic AD, about 99% of all cases). And now we have another
very rare mutation that has the opposite effect - so what? I know that
the  AD people are crowing about it
(http://www.alzforum.org/new/detail.asp?id=3209) but why? Again, more
than 99.9% of the elderly population, both with AD and without it,
don't have the mutation. If APP gene is almost always identical
between AD and healthy subjects, how could anybody claim that APP is
the *cause* (not a correlate) of AD? And the doubts go further:
Clearly, something affects amyloid processing in the elderly. A large
fraction of us will develop amyloid deposits. A large fraction of us
will become demented. Some of us will have both, some of us will have
neither, and some of us will have one but not the other. In other
words, APP gene mutations are not necessary for senile dementia to
occur, and amyloid accumulation is neither sufficient nor necessary
for dementia to occur. Removing amyloid or directly manipulating its
production by pharmacological means (gamma secretase inhibitors) have
completely and repeatedly failed in human studies - what else would a
non-biased person need to reject the idea that amyloid is the cause of


Rafal Smigrodzki, MD-PhD
Senior Scientist,
Gencia Corporation
706 B Forest St.

Charlottesville, VA 22903

tel: (434) 295-4800

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