Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System

Amyloid-β (Aβ) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral Aβ levels play in regulating Aβ brain clearance, we measured the clearance of [¹²⁵I]-Aβ_1–40 injected into the brains of liver-ligated rats that allowed peripheral Aβ levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Aβ_1–40. We found that elevating peripheral Aβlevels significantly decreased [¹²⁵]-Aβ_1–40 brain clearance, thus supporting the hypothesis that peripheral Aβ levels regulate Aβ clearance from the central nervous system.