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 (PrP(C)) in the mouse brain microvascular endothelial cell line MBEC4. TNFα decreased PrP(C) levels and intracellular radiolabeled Aβ. Similarly, anti-prion protein antibody also decreased radiolabeled Aβ. These results suggest that TNFα lowers PrP(C) levels, which in turn, reduces Aβ in the brain endothelium.

Keywords: Alzheimer’s disease; Beta-amyloid; Brain endothelial cell; Prion protein; Tumor necrosis factor-α.