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

Nobuya Kitaguchi, Harutsugu Tatebe, Kazuyoshi Sakai, Kazunori Kawaguchi, Shinji Matsunaga, Tomoko Kitajima, Hiroshi Tomizawa, Masao Kato, Satoshi Sugiyama, Nobuo Suzuki, Masao Mizuno, Hajime Takechi, Shigeru Nakai, Yoshiyuki Hiki, Hiroko Kushimoto, Midori Hasegawa, Yukio Yuzawa, Takahiko Tokuda

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)687-707
Number of pages21
JournalJournal of Alzheimer's Disease
Volume69
Issue number3
DOIs
Publication statusPublished - 01-01-2019

Fingerprint

Amyloidogenic Proteins
tau Proteins
Amyloid
Renal Dialysis
Alzheimer Disease
Brain
Therapeutics
Artificial Kidneys
Serum Amyloid A Protein
Immunoassay
Cerebral Cortex
Renal Insufficiency
Kidney

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Kitaguchi, Nobuya ; Tatebe, Harutsugu ; Sakai, Kazuyoshi ; Kawaguchi, Kazunori ; Matsunaga, Shinji ; Kitajima, Tomoko ; Tomizawa, Hiroshi ; Kato, Masao ; Sugiyama, Satoshi ; Suzuki, Nobuo ; Mizuno, Masao ; Takechi, Hajime ; Nakai, Shigeru ; Hiki, Yoshiyuki ; Kushimoto, Hiroko ; Hasegawa, Midori ; Yuzawa, Yukio ; Tokuda, Takahiko. / 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. In: Journal of Alzheimer's Disease. 2019 ; Vol. 69, No. 3. pp. 687-707.
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abstract = "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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Kitaguchi, N, Tatebe, H, Sakai, K, Kawaguchi, K, Matsunaga, S, Kitajima, T, Tomizawa, H, Kato, M, Sugiyama, S, Suzuki, N, Mizuno, M, Takechi, H, Nakai, S, Hiki, Y, Kushimoto, H, Hasegawa, M, Yuzawa, Y & Tokuda, T 2019, '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', Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 687-707. https://doi.org/10.3233/JAD-190087

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. / Kitaguchi, Nobuya; Tatebe, Harutsugu; Sakai, Kazuyoshi; Kawaguchi, Kazunori; Matsunaga, Shinji; Kitajima, Tomoko; Tomizawa, Hiroshi; Kato, Masao; Sugiyama, Satoshi; Suzuki, Nobuo; Mizuno, Masao; Takechi, Hajime; Nakai, Shigeru; Hiki, Yoshiyuki; Kushimoto, Hiroko; Hasegawa, Midori; Yuzawa, Yukio; Tokuda, Takahiko.

In: Journal of Alzheimer's Disease, Vol. 69, No. 3, 01.01.2019, p. 687-707.

Research output: Contribution to journalArticle

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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

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