Metallospecies and their biological functions in Alzheimer's disease.

This chapter critically explores the role of metallospecies homeostasis in the pathophysiology of Alzheimer's disease (AD), going beyond the traditional amyloid protein-centered approach. The discussion integrates biochemical, molecular, and analytical perspectives to elucidate how metal-biomolecule interactions influence protein misfolding, protein aggregation, and neurotoxicity. Furthermore, the chapter reviews cutting-edge metallomic approaches, including advanced speciation analyses and metal bioimaging techniques, to demonstrate how these tools allow for the precise characterization of the chemical identity, coordination environment, and spatial distribution of metal species in brain tissue. By discussing mechanistic insights with analytical advances, this chapter provides a comprehensive framework for understanding the contribution of metal dysregulation to AD and identifies new directions for diagnosis and therapeutic intervention.