The Association of Essential Metals with APOE Genotype in Alzheimer's Disease

Background: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ϵ4 of apolipoprotein E gene (APOE). It is proposed that ApoE, a protein involved in transport of cholesterol to neurons can cause neurodegeneration in AD through interaction with metals. Previous studies mostly associated copper, iron, zinc, and calcium with ApoE4-mediated toxicity. Objective: To test the association of essential metals with APOE genotype. Methods: We compared plasma and cerebrospinal fluid (CSF) levels of copper, zinc, iron, sodium, magnesium, calcium, cobalt, molybdenum, manganese, boron, and chromium, and CSF ferritin levels among AD, mild cognitive impairment (MCI) patients, and healthy controls (HC) with different APOE genotype. Results: Sodium, copper, and magnesium levels were increased in carriers of ϵ4 allele. Additionally, the increase in sodium, calcium and cobalt plasma levels was observed in carriers of ϵ4/ϵx genotype. The decrease in boron plasma levels was observed in carriers of ϵ4 allele and ϵ4/ϵ4 genotype. Additionally, CSF zinc levels as well as plasma sodium levels were increased in AD patients compared to HC. Conclusion: These results indicate that the molecular underpinnings of association of essential metals and metalloids with APOE should be further tested and clarified in vivo and in vitro.