An important paper. It would be good to have an exhaustive list of anticholinergics listed in order of their atropine equivalent effect.

View all comments by Paul Chabun

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. Beach, T.G., Kuo, Y.M., Spiegel, K, Emmerling, M.R., Sue, L.I., Kokjohn, K. and Roher, A.E. The cholinergic deficit coincides with AƒÒ deposition at the earliest histopathologic stages of Alzheimer¡¦s disease. J. Neuropath. Exp. Neurol. 59(4):308-13, 2000. Beach, T.G., Walker, D.G., Potter, P.E., Sue, L.I. and Fisher, A. Reduction of cerebrospinal fluid amyloid ƒÒ after systemic administration of M1 muscarinic agonists. Brain Res. 905:220-223, 2001. Beach, T.G., Kuo, Y.M., Schwab, C., Walker, D.G. and Roher, A.E. In vivo reduction of cortical amyloid ƒÒ after systemic administration of physostigmine. Neurosci. Lett. 310:21-24, 2001. Beach, TG, Walker, DG, Roher, AE and Potter, PE. Anti-amyloidogenic activity of cholinergic agents. Drug Dev Res 56, (2002) 242-247. Beach, TG. Muscarinic agonists as preventative therapy for Alzheimer¡¦s disease. Curr Opin Invest Drugs 3 (2002):1633-1636. Beach TG, D.G. Walker, P.E. Potter, L.I. Sue, S. Scott, K.J. Layne, A.J. Newell, P. K. Rauschkolb, M.E. Poston, S.D. Webster, R.A. Durham, M.R. Emmerling, W.G. Honer, A. Fisher and A.E. Roher. Immunotoxin lesion of the cholinergic nucleus basalis causes AƒÒ deposition: towards a physiologic animal model of Alzheimer¡¦s disease, Curr Med Chem 3:57-75, 2003.

View all comments by Thomas Beach