This is an important finding that adds to the human evidence pointing to a cholinergic-amyloid connection. Our group has contributed by showing that both muscarinic agonists and acetylcholinesterase inhibitors lower CSF and cortical ABeta levels in normal animals and both classes of drug also prevent the ABeta deposition induced experimentally by nucleus basalis lesion. It appears likely that the cortical cholinergic deficit associated with normal aging may be at least partially responsible for age-associated Abeta deposition and that cholinergic agents may be effective at preventing this. It is time for primary prevention trials of cholinergic agents for AD.
References:
Beach TG, Potter PE, Kuo YM, Emmerling MR, Durham RA, Webster SD, Walker DG, Sue LI, Scott S, Layne KJ, Roher AE.
Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition.
Neurosci Lett. 2000 Mar 31;283(1):9-12.
PubMed.
Beach TG, Kuo YM, Spiegel K, Emmerling MR, Sue LI, Kokjohn K, Roher AE.
The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease.
J Neuropathol Exp Neurol. 2000 Apr;59(4):308-13.
PubMed.
Beach TG, Walker DG, Potter PE, Sue LI, Fisher A.
Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonists.
Brain Res. 2001 Jun 29;905(1-2):220-3.
PubMed.
Beach TG, Kuo YM, Schwab C, Walker DG, Roher AE.
Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine.
Neurosci Lett. 2001 Sep 7;310(1):21-4.
PubMed.
Beach TG, Walker DG, Roher AE, Potter PE.
Anti-Amyloidogenic Activity of Cholinergic Agents.
Drug Dev Res. 2002;56 (2):242-47.
Beach TG.
Muscarinic agonists as preventative therapy for Alzheimer's disease.
Curr Opin Investig Drugs. 2002 Nov;3(11):1633-6.
PubMed.
Beach TG, Walker DG, Potter PE, Sue LI, Scott S, Layne KJ, Newell AJ, Rauschkolb PK, Poston ME, Webster SD, Durham RA, Emmerling MR, Honer WG, Fisher A, Roher AE.
Immunotoxin lesion of the cholinergic nucleus basalis causes Abeta deposition: towards a physiologic animal model of Alzheimer's disease.
Immunol Endocr Metab Agents Med Chem. 2003;3(1):57-75.
Comments
Peace Arch Hospital
An important paper.
View all comments by Paul ChabunIt would be good to have an exhaustive list of anticholinergics listed in order of their atropine equivalent effect.
Banner Sun Health Research Institute
This is an important finding that adds to the human evidence pointing to a cholinergic-amyloid connection. Our group has contributed by showing that both muscarinic agonists and acetylcholinesterase inhibitors lower CSF and cortical ABeta levels in normal animals and both classes of drug also prevent the ABeta deposition induced experimentally by nucleus basalis lesion. It appears likely that the cortical cholinergic deficit associated with normal aging may be at least partially responsible for age-associated Abeta deposition and that cholinergic agents may be effective at preventing this. It is time for primary prevention trials of cholinergic agents for AD.
References:
Beach TG, Potter PE, Kuo YM, Emmerling MR, Durham RA, Webster SD, Walker DG, Sue LI, Scott S, Layne KJ, Roher AE. Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition. Neurosci Lett. 2000 Mar 31;283(1):9-12. PubMed.
Beach TG, Kuo YM, Spiegel K, Emmerling MR, Sue LI, Kokjohn K, Roher AE. The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease. J Neuropathol Exp Neurol. 2000 Apr;59(4):308-13. PubMed.
Beach TG, Walker DG, Potter PE, Sue LI, Fisher A. Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonists. Brain Res. 2001 Jun 29;905(1-2):220-3. PubMed.
Beach TG, Kuo YM, Schwab C, Walker DG, Roher AE. Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine. Neurosci Lett. 2001 Sep 7;310(1):21-4. PubMed.
Beach TG, Walker DG, Roher AE, Potter PE. Anti-Amyloidogenic Activity of Cholinergic Agents. Drug Dev Res. 2002;56 (2):242-47.
Beach TG. Muscarinic agonists as preventative therapy for Alzheimer's disease. Curr Opin Investig Drugs. 2002 Nov;3(11):1633-6. PubMed.
Beach TG, Walker DG, Potter PE, Sue LI, Scott S, Layne KJ, Newell AJ, Rauschkolb PK, Poston ME, Webster SD, Durham RA, Emmerling MR, Honer WG, Fisher A, Roher AE. Immunotoxin lesion of the cholinergic nucleus basalis causes Abeta deposition: towards a physiologic animal model of Alzheimer's disease. Immunol Endocr Metab Agents Med Chem. 2003;3(1):57-75.
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