Deciphering the Significance of Metal Ions in the Pathogenesis of Alzheimer's Disease and Forging Pathways Towards Prospective Therapeutic Strategies

Abstract

Alzheimer’s disease (AD), a neurodegenerative condition, is characterized by its progressive cognitive decline, which includes memory impairment, language alterations, visuospatial challenges, and compromised executive functions. The primary pathological features of AD involve the formation of extracellular senile plaques primarily composed of β-amyloid (Aβ) and the accumulation of hyperphosphorylated tau proteins, leading to the creation of neurofibrillary tangles. With an aging global population and a lack of effective AD treatments, there is an urgent need for comprehensive AD research. Metallic elements like iron, zinc, copper, and manganese play essential roles in human development, metabolic pathways, and brain maturation. Accumulating evidence suggests that these metal ions significantly influence the development of AD, contributing to processes such as Aβ deposition, oxidative stress, neuroinflammatory responses, and disruptions in autophagy and apoptosis, among other cascading effects. Therefore, a thorough investigation into the relationship between metals and AD is crucial, not only to identify new pre-pathogenic interventions targeting metal ions but also to support the development of tailored AD treatments. This manuscript extensively explores the connection between metallic elements, specifically copper, iron, zinc, and manganese, in physiological processes and their intricate relationship with AD. It emphasizes the importance of understanding the regulation of the metal ion signaling network throughout the AD continuum to offer new perspectives and potential approaches for developing innovative metal ion modulators to combat AD. This research holds promise for addressing the global challenge of AD.