Alzheimer's Disease and diagnosis w/ tropicamide (fwd)

Jerry Clayton claytonj at essex.hsc.colorado.edu
Fri May 5 15:58:37 EST 1995


x011 at Lehigh.EDU wrote:
>In article <799465407snz at longley.demon.co.uk>, David Longley <David at longley.demo
>n.co.uk> writes:
>>In article <Pine.SGI.3.90.950501205152.10631A-100000 at umbc8.umbc.edu>
>>           rwashi1 at gl.umbc.edu "washington ryan" writes:
>>>>>>>>>>>>>>>>C U T >>>>>>>>>>>>>>>>>
>>> We give Alzheimer's patients medicine in an effort to increase their
>>> acetylcholine production.  They continue to decline.
>>>
>>> Perhaps, we should do the opposite.
>>>
>>> Give medicines to block acetylcholine transmission in the brain.  The
>>> brain should try to counteract the medicine by growing new acetylcholine
>>> connections and reduce the process of erasing acetylcholine processing
>>> sites.  When we take the medicine away a month later the patient should
>>> be performing at significantly higher levels of cognitive functions.
>>> Ron Blue x011 at lehigh.edu
>>>
>>Wouldn't this  be akin to  giving  diabetics insulin receptor blockers, and
>>parkinson's patients Dopamine receptor blockers in the hope that they would
>>get better? I see the reasoning re: receptor supersensitivity etc, but ....
>>--
>>David Longley
>>
>Yes, supersensitivity and possibly increase in receptor sites for
>acetylcholine.  If you have the model (GRIN!) of a bucket full of
>water with a metal rod stuck in it and you are vibrating the bucket
>at a particular frequency the metal rod messes up the waves on
>the water.  If you could use another procedure you may be able to
>get a wave pattern that would normalize AS IF there were no metal rod
>in the bucket.
>The metal rod is symbolic of the process that lead to the destruction
>of the hypocampus.
>Using acetylcholine blockers may force the brain to destroy the area
>destroying the hypocampus and increase in number of acetylcholine
>receptor sites.
>When the acetylcholine blocker is removed the brain is functioning
>at a more normal level.
>Ron Blue x011 at lehigh.edu
>
The analogy to Parkinson's disease and DA receptor supersensitivity
is likely very pertinent here however, the nigral DA system and the
basal forebrain cholinergic system function very differently.  Whereas
DA functions somewhat nonspecifically and seems to "bias" the striatum
to handle cortical input, Ach from the basal forebrain may need to be 
very specific in terms of connectivity.  This could give some
explanation why cholinergic drugs don't appear to help in AD.  I feel
it likely too that feeding a dying population of cholinergic neurons
precursors will eventually quit working as in Parkinson's and L-dopa
because too few neurons are available to provide the neurotransmitter.
Ryan stated in the original post that he was giving patients drugs to 
enhance Ach production.  For the reasons I just indicated it may be 
that not enough neurons are available to provide the Ach and the 
distribution of the neurotransmitter may not be specific enough.  I 
believe that directly acting cholinergic drugs may provide some 
symptomologic relief but would do little to address the problem of 
cell death of course.  Anticholinesterases may work in the short run
but again would have limited effects in the latter stages of disease
when the Ach population becomes small.  Got to admit though, Rons idea
is kind of interesting though.  Got that model worked out yet?
Chuckle!  Interesting thread!
Jerry Clayton
claytonj at essex.hsc.colorado.edu





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