Tumor necrosis factor-α reduces beta-amyloid accumulation primarily by lowering cellular prion protein levels in a brain endothelial cell line

Abstract

Disruption of beta-amyloid (Aβ) transport across the blood–brain barrier is thought to cause Aβ accumulation in the brain, thus leading to the development of Alzheimer’s disease (AD). As AD patients show increased serum tumor necrosis factor-α (TNFα) levels, we examined the effect of TNFα on the function and expression of Aβ transport-related proteins including cellular prion protein (PrPC) in the mouse brain microvascular endothelial cell line MBEC4. TNFα decreased PrPC levels and intracellular radiolabeled Aβ. Similarly, anti-prion protein antibody also decreased radiolabeled Aβ. These results suggest that TNFα lowers PrPC levels, which in turn, reduces Aβ in the brain endothelium.