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.