Muscarinic agonists as preventative therapy for Alzheimer's disease.

Overproduction of the peptide amyloid beta (Abeta) is a critical pathogenic event in Alzheimer's disease (AD), leading to the formation of amyloid plaques, neurofibrillary tangles, synaptic loss and dementia. Decreasing Abeta production may therefore slow or halt the progression of AD. Recent animal experiments suggest that Abeta overproduction in aging and sporadic AD may be due to age-related loss of cortical cholinergic innervation. Muscarinic agonists, particularly M1-selective agents, have been shown to decrease the production of Abeta in vitro and in vivo; these compounds may be uniquely suited to a preventative role in AD therapy.