β-amyloid peptides as direct cholinergic neuromodulators:: a missing link?

beta-Amyloid peptide (A beta) is found in diffuse and focal deposits throughout the brain from Alzheimer's disease (AD) patients. Another feature of AD is the widespread degeneration and dysfunction of the basal-forebrain cholinergic system. Until now, it has been unclear how these features of AD might be related. Recent reports, however, suggest that A beta can potently inhibit various cholinergic neurotransmitter functions independently of apparent neurotoxicity. This capacity of AP might contribute to the vulnerability of selected cholinergic neuronal populations in AD. Moreover, the high potency (picomolar to nanomolar concentrations) of these effects and the secretion of A beta by brain cells indicate that A beta-induced cholinergic hypoactivity might have physiological in addition to pathological significance.