A key neuropathological hallmark of Alzheimer's disease (AD) is amyloid-� (A�) plaques in the brain. The mechanisms driving formation of these protein aggregates and their causal link to dementia are still unclear. An additional observation in the AD brain is the accumulation of metal ions, which has been proposed to be associated with Ab aggregates and neuronal death, yet relatively little is known. Even through a large body of continuously reported literature regarding metal ions and A� species, direct connection of metal-A� interaction with AD onset and development has been neglected in this field due to lack of appropriate tools and/or tactics. Therefore, we have developed chemical tools and/or tactics that are capable of specifically targeting metal-associated A� species and modulating their interaction and reactivity. Here, our rational structure-based design principle and recent findings for chemical tools and tactics for investigating metal-A� chemistry and biology in AD will be discussed.

Chemical tools and tactics to study the role of metal-associated misfolded proteins in human neurodegenerative diseases

245th National Meeting (2013)

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