TY - JOUR
T1 - Influx of Tau and Amyloid-β Proteins into the Blood during Hemodialysis as a Therapeutic Extracorporeal Blood Amyloid-β Removal System for Alzheimer's Disease
AU - Kitaguchi, Nobuya
AU - Tatebe, Harutsugu
AU - Sakai, Kazuyoshi
AU - Kawaguchi, Kazunori
AU - Matsunaga, Shinji
AU - Kitajima, Tomoko
AU - Tomizawa, Hiroshi
AU - Kato, Masao
AU - Sugiyama, Satoshi
AU - Suzuki, Nobuo
AU - Mizuno, Masao
AU - Takechi, Hajime
AU - Nakai, Shigeru
AU - Hiki, Yoshiyuki
AU - Kushimoto, Hiroko
AU - Hasegawa, Midori
AU - Yuzawa, Yukio
AU - Tokuda, Takahiko
N1 - Funding Information:
The authors thank Ms. Miwa Sakata for her technical assistance and Drs. Takao Senda and Ryuji Hata for their support to obtain brain samples. This work was partly supported by KAKENHI (20509008, 23500531, 26282126), and the Smoking Research Foundation.
Publisher Copyright:
© 2019 - IOS Press and the authors. All rights reserved.
PY - 2019
Y1 - 2019
N2 - The accumulation of amyloid-β protein (Aβ) and tau in the brain is a major pathological change related to Alzheimer's disease. We have continued to develop Extracorporeal Blood Aβ Removal Systems (E-BARS) as a method for enhancing Aβ clearance from the brain. Our previous report revealed that dialyzers effectively remove blood Aβ and evoke large Aβ influxes into the blood, resulting in a decrease in brain Aβ accumulation after initiating hemodialysis, and that patients who underwent hemodialysis had lower brain Aβ 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 Aβ but not extracorporeal blood tau. The influx of tau into the blood was observed at around the 1h period during hemodialysis sessions. However, the influx amount of tau was far smaller than that of Aβ. 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 Aβ migration into the blood. However, as a therapeutic strategy for Alzheimer's disease, it may only be effective for removing Aβ from the brain.
AB - The accumulation of amyloid-β protein (Aβ) and tau in the brain is a major pathological change related to Alzheimer's disease. We have continued to develop Extracorporeal Blood Aβ Removal Systems (E-BARS) as a method for enhancing Aβ clearance from the brain. Our previous report revealed that dialyzers effectively remove blood Aβ and evoke large Aβ influxes into the blood, resulting in a decrease in brain Aβ accumulation after initiating hemodialysis, and that patients who underwent hemodialysis had lower brain Aβ 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 Aβ but not extracorporeal blood tau. The influx of tau into the blood was observed at around the 1h period during hemodialysis sessions. However, the influx amount of tau was far smaller than that of Aβ. 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 Aβ migration into the blood. However, as a therapeutic strategy for Alzheimer's disease, it may only be effective for removing Aβ from the brain.
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U2 - 10.3233/JAD-190087
DO - 10.3233/JAD-190087
M3 - Article
C2 - 31156161
AN - SCOPUS:85067101948
VL - 69
SP - 687
EP - 707
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -