i appreciate your contributions ZF and you were the first one that pointed out what anticholinergic drugs are for and why pwp take them. I have questions - just barely comprehending the point of each abstract, i'll try to ask them in a way that would take a brief answer if possible. starting with your first post:

Results: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = –12%) (false discovery rate–corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = –27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced.

Conclusions: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.

Does that mean our acetylcholinesterase, or AChE is dysfunctional ?[recalling here that pesticide toxins bind to AChE and damage them] thus causing a build up of too much acetylcholine because the inhibitor isn't breaking it down?

Is that what they mean by "regional AChE activity in the brain was reduced. '?

Is brain cholinergic dysfuction a term that can be applied interchangeably to a lack of AChE inhibition and break down of acetylcholine as well as a need for more acetylcholine because....??? the AChE is defective,? gone? we take too much artane? what causes the lack of acetylcholine? would that solve alzheimers and is it a question that can't be answered yet?

we take anticholinergic drugs. does that mean cholinergic enhances acetylcholine and anticholinergic works to break it down?


next post:
We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer’s disease (AD).

If we are losing the inhibitor AChE that breaks acetylcholine down, why would we take cholinergic drugs like aricept that would inhibit the breakdown of acetylcholine even more?

Fox post:
Conclusions: Although the majority of patients with PD have evidence of a robust parallel decline in striatal dopaminergic and cortical cholinergic activity, there is a subgroup (19.1%) of patients with decreased dopaminergic but preserved cholinergic activity.

What isn't working in "cortical cholinergic activity"? Does this mean as we progress, we inhibit and break down acetylcholine less? Is too much acetylcholine working against the dopamine because the AChE activity declines and there is no breakdown of acetylcholine?

I keep going back to Ron's saying 'one pushes and the other pull." not when one isn't working....then could they both push or pull....it certainly sounds like a struggle to maintain our balance.


last post:
The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3′ alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membrane-association patterns.

Differentially induced under stress, they show distinct non-hydrolytic properties and interact with different protein partners. Recent findings suggest that transcriptional and post-transcriptional regulation of AChE pre-mRNA is a neuroprotection strategy but might involve long-term damage.

Specifically, variant-specific causal involvement of AChE in the progression of both neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) and neuromuscular syndromes (e.g. myasthenia gravis) raises the possibility that future therapeutic drugs might target specific AChE variant(s) or the corresponding RNA transcripts.

Not sure i understand this one. what is post -transcriptional regulation of AChE and is it actually saying that neuroprotective strategies can cause long term damage?

hmmm.....is it me?

adding after more thought. is it basically saying that here is some evidence that stress causes brain damage - in this case by releasing too much AChE inhibitor? again---in waay over my head and this is a question.

thanks ZF,
paula