This article is so confusing it's funny, but I think they are answering my probing question about AD and PD taking cholinesterase inhibitors.
I think this article says that when anti-cholinesterase drugs [Aricept] are given to a person with a cholinesterase deficiency [polymorphism? gene?] it can cause it to overexpress the enzyme, resulting in pools of extra enzyme.

Researchers who are multi lingual and speak this language feel free to add.

http://hmg.oxfordjournals.org/cgi/content/full/9/9/1273

One of the last sentences says,

"To conclude, this polymorphism, identifies a new HNF3-binding enhancer domain important for AChE expression. Heterozygosity for the deletion is manifested as constitutive overproduction of AChE;

such overproduction, which increases the susceptibility to acute anti-AChE exposures in mice, [ surely this increases acetylcholine?] is likely to be the cause of the hypersensitivity of proband I to pyridostigmine.

pyridostigmine is anticholinesterase [like Aricept]

The proposed link between this mutation and the hypersensitivity points to carriers of this allele [gene?]as individuals at risk of developing adverse responses under treatment with or exposure to anti-AChEs, which is important in view of the increasing use of anti-AChEs as Alzheimer’s disease drugs (11).

Moreover, stress- or anti-AChE-induced increases in AChE levels (17) may cause acquired anti-AChE sensitivity, putting at risk a considerably wider group of individuals (7).

This type of chemical hypersensitivity therefore emerges from our study as a complex trait, perhaps involving both early modulators such as transcription factors and downstream responding genes."

So messing with the enzyme can ruin its function,which can cause permanent sensitivity problems and dysfunction. It's an overproduction of the enzyme, but rather than flowing freely it collects, but i'm left with the same question:

Is the result of this an increase in acetycholine? Is the bottom line still too much acetylcholine? or does the trouble stop at the pool of enzyme spillage? i doubt the latter. Does anyone know?


It isn't as cut and dry as i thought when starting this research but now i know more about what leads to a similar reaction as mine when trying aricept. From what I can tell, the results are delivering the same message. It's risky to take this type of drugs if you have alzheimers or pd. It interferes and interrupts the break down of acetylcholine, which is toxic if givven too large a quantity. These drugs whose purpose is to provide greater quantities of acetylcholine for cognition cause overexpression of the enzyme inhibitor AChE which collects in pools. Collecting in pools sounds ominous.

thanks!
paula