Journal of Artificial Organs

, Volume 21, Issue 2, pp 220–229 | Cite as

Adsorptive filtration systems for effective removal of blood amyloid β: a potential therapy for Alzheimer’s disease

  • Nobuya Kitaguchi
  • Kazunori Kawaguchi
  • Kazunori Yamazaki
  • Hiroshi Kawachi
  • Miwa Sakata
  • Megumi Kaneko
  • Masao Kato
  • Kazuyoshi Sakai
  • Norimi Ohashi
  • Midori Hasegawa
  • Yoshiyuki Hiki
  • Yukio Yuzawa
Original Article Apheresis


Accumulation of amyloid-β protein (Aβ) in the brain causes cognitive impairment in Alzheimer’s disease. We hypothesized that an extracorporeal system that rapidly removed Aβ from the blood may accelerate Aβ drainage from the brain. We previously reported that dialyzers remove blood Aβs effectively, mainly by adsorption on the inner surfaces of the hollow fibers, resulting in lower Aβ accumulation in the brains of patients undergoing hemodialysis than the controls without hemodialysis. The aim of the present study was to create a more convenient and effective blood Aβ removal system using adsorptive filtration, in which the filtrate returned to the body. Filtration from inside to outside of the fibers may enhance the adsorption of plasma Aβs on the surface of micropores inside the hollow fiber walls. Hence, pool solutions of 4 ng/mL synthetic Aβ1–40 and Aβ1–42 peptides (300 mL) or human plasma (1000 mL of 250–346 pg/mL Aβ1–40 and 30–48 pg/mL Aβ1–42) were circulated through polysulfone dialyzers at a flow rate of 50 mL/min to evaluate an adsorptive filtration system. The rates of Aβ reduction from the pool solutions significantly increased along with the filtration rates. A filtration rate of > 1 mL/min, preferably 5–10 mL/min resulted in an 80–100% reduction of Aβs within 30 min of circulation. The rates of Aβs passing through the membrane walls were maintained around 0% for plasma Aβs during circulation. Thus, our adsorptive filtration systems may be useful for removing blood Aβs for patients with Alzheimer’s disease.


Adsorptive filtration system Alzheimer’s disease Amyloid-β Aβ Dialyzer 



The authors thank Moe Kobayakawa, Miki Kamiya, Yuna Kato, Yumi Baba, Hitomi Shima, Tatsuya Hama, and Masahito Mizuno for their technical assistance. This work was partly supported by KAKENHI (23500531 and 26282126) and the Smoking Research Foundation.

Compliance with ethical standards

Conflict of interest

Nobuya Kitaguchi has stock ownership in Asahi Kasei Corporation Co., Ltd. The other authors declare that they have no conflict of interest.


  1. 1.
    Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ. Naturally secreted oligomers of amyloid b protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Hung LW, Ciccotosto GD, Giannakis E, Tew DJ, Perez K, Masters CL, Cappai R, Wade JD, Barnham KJ. Amyloid-β peptide (Aβ) neurotoxicity is modulated by the rate of peptide aggregation: Aβ dimers and trimers correlate with neurotoxicity. J Neurosci. 2008;28:11950–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased clearance of CNS β-amyloid in Alzheimer’s disease. Science. 2010;330:1774.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O’Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537:50–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Boada M, Ortiz P, Anaya F, Hernández I, Muñoz J, Núñez L, Olazarán J, Roca I, Cuberas G, Tárraga L, Buendia M, Pla RP, Ferrer I, Páez A. Amyloid-targeted therapeutics in Alzheimer’s disease: use of human albumin in plasma exchange as a novel approach for Aβ mobilization. Drug News Perspect 2009:22;325–39.Google Scholar
  7. 7.
    Kawaguchi K, Kitaguchi N, Nakai S, Murakami K, Asakura K, Mutoh T, Fujita Y, Sugiyama S. Novel therapeutic approach for Alzheimer’s disease by removing amyloid-β protein from the brain with an extracorporeal removal system. J Artif Organs. 2010;13:31–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Kitaguchi N, Kawaguchi K, Nakai S, Murakami K, Ito S, Hoshino H, Hori H, Ohashi A, Shimano Y, Suzuki N, Yuzawa Y, Mutoh T, Sugiyama S. Reduction of Alzheimer’s Disease Amyloid-β in plasma by hemodialysis and its relation to cognitive functions. Blood Purif. 2011;32:57–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Kato M, Kawaguchi K, Nakai S, Murakami K, Hori H, Ohashi A, Hiki Y, Ito S, Shimano Y, Suzuki N, Sugiyama S, Ogawa H, Kusimoto H, Mutoh T, Yuzawa Y, Kitaguchi N. Potential therapeutic system for Alzheimer’s disease: removal of blood Abs by hemodialyzers and its effect on the cognitive functions of renal-failure patients. J Neural Transm. 2012;119:1533–44.CrossRefPubMedGoogle Scholar
  10. 10.
    Kitaguchi N, Hasegawa M, Ito S, Kawaguchi K, Hiki Y, Nakai S, Suzuki N, Shimano Y, Ishida O, Kushimoto H, Kato M, Koide S, Kanayama K, Kato T, Ito K, Takahashi H, Mutoh T, Sugiyama S, Yuzawa Y. A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis: a potential therapeutic strategy for Alzheimer’s disease. J Neural Transm. 2015;122:1593–607.CrossRefPubMedGoogle Scholar
  11. 11.
    Sakai K, Senda T, Hata R, Kuroda M, Hasegawa M, Kato M, Abe M, Kawaguchi K, Nakai S, Hiki Y, Yuzawa Y, Kitaguchi N. Patients that have undergone hemodialysis exhibit lower amyloid deposition in the brain: evidence supporting a therapeutic strategy for Alzheimer’s disease by removal of blood amyloid. J Alzheimer Dis. 2016;51:997–1002.CrossRefGoogle Scholar
  12. 12.
    Kawaguchi K, Saigusa A, Yamada S, Gotoh T, Nakai S, Hiki Y, Hasegawa M, Yuzawa Y, Kitaguchi N. Toward the treatment for Alzheimer’s disease: Adsorption is primary mechanism of removing amyloid β protein with hollow-fiber dialyzers of the suitable materials, Polysulfone and polymethyl methacrylate. J Artif Organs. 2016;19:149–58.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2017

Authors and Affiliations

  1. 1.Faculty of Clinical Engineering, School of Health ScienceFujita Health UniversityToyoakeJapan
  2. 2.Graduate School of Medicine, Nephrology of ScienceFujita Health UniversityToyoakeJapan
  3. 3.Ogaki Municipal HospitalOgakiJapan
  4. 4.Department of Nephrology, School of MedicineFujita Health UniversityToyoakeJapan
  5. 5.Iwata City HospitalIwataJapan

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