Influx of Tau and Amyloid-ß Proteins into the Blood During Hemodialysis as a Therapeutic Extracorporeal Blood Amyloid-ß Removal System for Alzheimer's Disease.

ABSTRACT

The accumulation of amyloid-ß protein (Aß) and tau in the brain is a major pathological change related to Alzheimer's disease. We have continued to develop Extracorporeal Blood Aß Removal Systems (E-BARS) as a method for enhancing Aß clearance from the brain. Our previous report revealed that dialyzers effectively remove blood Aß and evoke large Aß influxes into the blood, resulting in a decrease in brain Aß accumulation after initiating hemodialysis, and that patients who underwent hemodialysis had lower brain Aß accumulation than those who did not. Here, plasma total tau concentrations from 30 patients undergoing hemodialysis were measured using an ultrasensitive immunoassay and compared to those from 11 age-matched controls. Plasma total tau concentrations were higher in patients with renal failure regardless of whether they underwent hemodialysis, suggesting the involvement of the kidneys in tau degradation and excretion. Hemodialyzers effectively removed blood Aß but not extracorporeal blood tau. The influx of tau into the blood was observed at around the 1 h period during hemodialysis sessions. However, the influx amount of tau was far smaller than that of Aß. Furthermore, histopathological analysis revealed similar, not significantly less, cerebral cortex phosphorylated tau accumulation between the 17 patients who underwent hemodialysis and the 16 age-matched subjects who did not, although both groups showed sparse accumulation. These findings suggest that hemodialysis may induce both tau and Aß migration into the blood. However, as a therapeutic strategy for Alzheimer's disease, it may only be effective for removing Aß from the brain.