Trace concentrations, heavy implications: Influences of biometals on major brain pathologies of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative condition that involves accumulation of toxic protein species, notably amyloid-β (Aβ)plaques and neurofibrillary tau tangles that are associated with cognitive decline. These proteins can bind metal ions, ultimately affecting their structure and function. In this review, we discuss key biometals such as zinc, copper, and iron that interact with protein species involved in AD, mainly Aβ, tau, and the late-onset AD risk factor Apolipoprotein E (APOE). These metals interact with Aβ and tau proteins, affecting their aggregation and toxicity. The allele variants of APOE also have different interactions with these metals, affecting APOE protein expression and aggregation of AD protein species.