Toward the treatment for Alzheimer's disease: adsorption is primary mechanism of removing amyloid beta protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate

摘要

The accumulation of amyloid beta protein (A beta) in the brain reflects cognitive impairment in Alzheimer's disease. We hypothesized that the rapid removal of A beta from the blood by an extracorporeal system may act as a peripheral A beta sink from the brain. The present study aimed to determine the optimal materials and modality for A beta removal by hemodialyzers. In a batch analysis, hollow-fiber fragments of polysulfone (PSf) and polymethyl methacrylate (PMMA) showed greater removal efficiency of A beta than did other materials, such as cellulose-triacetates and ethylene-vinyl alcohol copolymer (PSf: PMMA at 30 min, 98.6 +/- 2.4 %: 97.8 +/- 0.4 % for A beta(1-40) and 96.6 +/- 0.3 %: 99.0 +/- 1.0 % for A beta(1-42)). In a modality study, the A beta solution was applied to PSf dialyzers and circulated in the dialysis and Air-filled adsorption-mode (i.e., the outer space of the hollow fibers was filled with air) or phosphate-buffered saline (PBS)-filled adsorption modes. The A beta(1-40) removal efficiency of the pre/post dialyzer in the Air-filled adsorption-mode was the highest (62.4 +/- 12.6 %, p = 0.007). In a flow rate study in the Air-filled adsorption-mode, 200 mL/min showed the highest A beta(1-40) reduction rate of pool solution (97.3 +/- 0.8 % at 15 min) compared with 20 mL/min (p = 0.00001) and 50 mL/min (p = 0.00382). PMMA dialyzers showed similar high reduction rates. Thus, the optimal modality for A beta removal was the adsorption-mode with PSf or PMMA hollow fibers at around 50 mL/min flow rate, which seems to be suitable for clinical use.