Neuronal receptors as targets for the action of amyloid-beta protein (Aβ) in the brain

Accumulation of neurotoxic soluble amyloid-beta protein (A beta) oligomers in the brains of patients with Alzheimer disease (AD) and their role in AD pathogenesis have emerged as topics of considerable interest in recent years. Soluble A beta oligomers impair synaptic and neuronal function, leading to neurodegeneration that is clinically manifested by memory and cognitive dysfunction. The precise mechanisms whereby A beta oligomers cause neurotoxicity remain unknown. Emerging insights into the mechanistic link between neuronal receptors and soluble A beta oligomers highlight the potential role of these receptors in A beta-mediated neurotoxicity in AD. The current review focuses on studies describing interactions between soluble A beta oligomers and neuronal receptors, and their role in AD pathogenesis. Furthermore, these studies provide insight into potential therapies for AD using compounds directed at putative target receptors for the action of A beta in the central nervous system. We focus on interactions of A beta with subtypes of acetylcholine and glutamatergic receptors. Additionally, neuronal receptors such as insulin, amylin and receptor for advanced glycation end products could be potential targets for soluble A beta-oligomer-mediated neurotoxicity. A beta interactions with other receptors such as the p75 neurotrophin receptors, which are highly expressed on cholinergic basal forebrain neurons lost in AD, are also highlighted.