EXTRACORPOREAL BLOOD Aβ REMOVAL SYSTEM (EBARS) REDUCED SOLUBLE Aβ IN THE BRAIN BY TRIGGERING INFLUX INTO THE BLOOD: RAT STUDIES

Abstract

Rapid removal of Aβ from the blood by an extra-corporeal system may act as a peripheral sink from the brain. We have reported that 1) several medical materials including hemodialyzers are able to remove Aβ effectively, 2) the concentrations of blood Aβs decreased and Aβ influx into blood were triggered during hemodialysis in humans, 3) Aβ deposition in the brain of hemodialysis patients was significantly lower than controls. Here, the effect of removing blood Aβ on blood and cerebrospinal fluid (CSF) concentrations of Aβ was investigated in rats. This study was approved by the Institutional Animal Care and Use Committee in Education and Research Center of Fujita Health University. The blood of normal SD male rats (9–11weeks, n=8) was treated for 60 minutes extracorporeally with mini-columns of hexadecyl-alkylated cellulose beads (HDC) as Aβ removers. Blood was collected at pre/post of the HDC-columns and CSF from Cisterna magna. The Aβ1–40 and Aβ1–42concentrations were measured by sandwich ELISAs (WAKO, Japan). The removal efficiencies of the blood Aβs by HDC-columns were 98% at 30min and 83% at 60min for Aβ1–40, 96% at 30min and 94% at 60min for Aβ1–42 during blood purification. Despite such high removal efficiencies, the blood Aβ concentrations at the end of blood Aβs removal (60min) in the whole body circulation significantly “increased” up to 153% for Aβ1–40 and 187% for Aβ1–42 (both, p=0.0003) compared with those just before the treatment. Further, Aβ concentrations in CSF decreased to 77% for Aβ1–40 (p=0.022) and 90% for Aβ1–42 (p=0.27). The decrease tendency of CSF Aβs continued another 60min; 64% for Aβ1–40 (p=0.071) and 77% for Aβ1–42 (p=0.25) compared with those before the treatment. Removal blood Aβ may trigger the influx from the brain into the blood. This might explain few Aβ depositions in the brains of hemodialysis patients. Therefore, Extracorporeal Blood Aβ Removal Systems may be potential therapeutic systems for Alzheimer's Disease. Acknowledgment: The authors thank Mrs. Kota Watanabe, Hiroki Aoki, and Ms. Yuri Sakakibara for their technical assistance. This work was partly supported by KAKENHI (2350531, 26282126) and Smoking Research Foundation.