Cholesterol and metal ions in Alzheimer's disease

Cholesterol and metal ions have been suggested to be associated with the onset and progression of Alzheimer's disease (AD). Moreover, recent findings have demonstrated a potential interconnection between these two factors. For example, (a) cholesterol has been shown to be misregulated in AD-afflicted brains, and the aberrant activity of proteins (particularly, apolipoprotein E (ApoE) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)) has been linked to cholesterol-related AD exacerbation; (b) dyshomeostasis of metal ions associated with misfolded proteins (i.e., amyloid-β (Aβ) aggregates) found in the brains of AD patients is shown to promote oxidative stress leading to the malfunction of multiple proteins, including cytochrome c oxidase (CcO), and Cu/Zn superoxide dismutase (SOD1); (c) metal ion misregulation has also been observed to disrupt the activity of proteins (e.g., HMGR, low-density lipoproteins (LDL)), required for cholesterol production and regulation. Herein, we briefly discuss the potential involvement of cholesterol and metal ions in AD neuropathogenesis in both individual and interrelated manners.