Chemical (Bioinorganic) Strategies to Study Multiple Facets in Dementia

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive loss of neurons and synapses, leading to cognitive and motor impairment and ultimately death. Multiple interconnected pathological factors contribute to AD, including (i) aggregation of amyloid-β (Aβ) peptides into plaques, (ii) metal ion dyshomeostasis and miscompartmentalization, and (iii) inflammation and oxidative stress driven by excessive reactive oxygen species (ROS). Metals are frequently detected within Aβ plaques and are thought to promote Aβ neurotoxicity and redox activity, while ROS can accelerate Aβ aggregation. Despite increasing evidence linking these processes, the mechanistic relationships among them remain poorly understood. Current AD therapies primarily provide symptomatic relief by addressing cholinergic deficits, rather than targeting the underlying multifactorial pathology. To address this challenge, we have developed chemical tools that simultaneously modulate multiple pathogenic factors and probe the interaction networks formed by metals, Aβ, and oxidative processes in AD.