The Ongoing Search for Small Molecules to Study Metal-AssociatedAmyloid-β Species in Alzheimer’s Disease.

The development of a cure for Alzheimer’sdisease (AD) hasbeen impeded by an inability to pinpoint the root cause of this disorder.Although numerous potential pathological factors have been indicated,acting either individually or mutually, the molecular mechanisms leadingto disease onset and progression have not been clear. Amyloid-β(Aβ), generated from proteolytic processing of the amyloid precursorprotein (APP), and its aggregated forms, particularly oligomers, aresuggested as key pathological features in AD-affected brains. Historically,highly concentrated metals are found colocalized within Aβ plaques.Metal binding to Aβ (metal–Aβ) generates/stabilizespotentially toxic Aβ oligomers, and produces reactive oxygenspecies (ROS) in vitro (redox active metal ions; plausible contributionto oxidative stress). Consequently, clarification of the relationshipbetween Aβ, metal ions, and toxicity, including oxidative stressvia metal–Aβ, can lead to a deeper understanding of ADdevelopment. [ABSTRACT FROM AUTHOR]