The association of APOE-ε4 with Alzheimer’s disease could be due to a connection of APOE-ε4 with selenium transport into cells.

Carriers of of the apoE ε4 allele have significantly lower selenium levels in nails and brains. Selenoprotein P is a selenium transport protein. Apolipoprotein E receptor 2 by binding to selenoprotein P regulates uptake of selenium into cells. Both apolipoprotein E receptor 2 and apolipoprotein E regulate transport of selenoprotein P into cells. Selenoprotein P provides protection from amyloid β (Aβ), the main component of amyloid plaques seen in Alzheimer’s disease. The association of apoE ε4 with Alzheimer’s disease could be due to apoE ε4 not being as effective in regulation of selenium transport into cells via apolipoprotein E receptor 2 as other alleles of apoE.

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