Adsorptive filtration systems for effective removal of blood amyloid β: a potential therapy for Alzheimer’s disease

Accumulation of amyloid-β protein (Aβ) in the brain causes cognitive impairment in Alzheimer’s disease. We hypothesized that an extracorporeal system that rapidly removed Aβ from the blood may accelerate Aβ drainage from the brain. We previously reported that dialyzers remove blood Aβs effectively, mainly by adsorption on the inner surfaces of the hollow fibers, resulting in lower Aβ accumulation in the brains of patients undergoing hemodialysis than the controls without hemodialysis. The aim of the present study was to create a more convenient and effective blood Aβ removal system using adsorptive filtration, in which the filtrate returned to the body. Filtration from inside to outside of the fibers may enhance the adsorption of plasma Aβs on the surface of micropores inside the hollow fiber walls. Hence, pool solutions of 4 ng/mL synthetic Aβ_1–40 and Aβ_1–42 peptides (300 mL) or human plasma (1000 mL of 250–346 pg/mL Aβ_1–40 and 30–48 pg/mL Aβ_1–42) were circulated through polysulfone dialyzers at a flow rate of 50 mL/min to evaluate an adsorptive filtration system. The rates of Aβ reduction from the pool solutions significantly increased along with the filtration rates. A filtration rate of > 1 mL/min, preferably 5–10 mL/min resulted in an 80–100% reduction of Aβs within 30 min of circulation. The rates of Aβs passing through the membrane walls were maintained around 0% for plasma Aβs during circulation. Thus, our adsorptive filtration systems may be useful for removing blood Aβs for patients with Alzheimer’s disease.