Advances on metal elements and mechanisms of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease and also the leading cause of dementia. The over-expression and deposition of amyloid β (Aβ) and the hyperphosphorylated Tau protein play critical roles in the pathogenesis of AD. However, the underlying mechanisms of AD are complex and still not fully understood. In recent years, increasing studies have found that changes of metal element levels in the body are closely associated with the progression of AD. Metal elements could regulate the production and deposition of Aβ in the brain by affecting the expression and activities of proteins related to the production, transport, and metabolism of Aβ. In addition, metal elements also play an important role in the progression of AD by regulating the hyperphosphorylation of tau protein. In this review, we summarized the roles of four metal elements including copper, aluminum, iron, and lead in the development of AD, and illustrated their mechanisms in Aβ over-expression and Tau protein hyperphosphorylation, aiming to provide new sights and a theoretical basis for the prevention and treatment of AD.