A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis: a potential therapeutic strategy for Alzheimer’s disease

Nobuya Kitaguchi, Midori Hasegawa, Shinji Ito, Kazunori Kawaguchi, Yoshiyuki Hiki, Sigeru Nakai, Nobuo Suzuki, Yasunobu Shimano, Osamu Ishida, Hiroko Kushimoto, Masao Kato, Sigehisa Koide, Kyoko Kanayama, Takashi Kato, Kengo Ito, Hiroshi Takahashi, Tatsuro Mutoh, Satoshi Sugiyama, Yukio Yuzawa

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

To obtain the proof of concept of a novel therapy for Alzheimer’s disease (AD), we conducted two prospective studies with hemodialysis patients who had amyloid β protein (Aβ) removed from their blood three times a week. One major pathological change in the brain associated with AD is Aβ deposition, mainly 40 amino acids Aβ1–40 and 42 amino acids Aβ1–42. Impaired Aβ clearance is proposed to be one cause of increased Aβ in the AD brain. Thus, we hypothesized that an extracorporeal removal system of Aβ from the blood may remove brain Aβ and be a useful therapeutic strategy for AD. In the first prospective study, plasma Aβ levels and the cognitive function of 30 hemodialysis patients (65–76 years old) were evaluated at baseline as well as 18 or 36 months after. Although plasma Aβ1–40 levels either decreased or remained unchanged, levels of Aβ1–42 either remained unchanged or increased at the second time point. Mini-Mental State Examination scores of most subjects increased or were maintained at the second time point. Aβ1–40 influx into the blood correlated with MMSE at the second time point. In the second prospective study, five patients (51–84 years old) with renal failure were evaluated before and after the initiation of hemodialysis. Plasma Aβ levels decreased, while cognitive function improved after initiating blood Aβ removal. Therefore, long-term hemodialysis, which effectively removes blood Aβ, might alter Aβ influx and help maintain cognitive function.

Original languageEnglish
Pages (from-to)1593-1607
Number of pages15
JournalJournal of Neural Transmission
Volume122
Issue number11
DOIs
Publication statusPublished - 01-11-2015

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Cognition
Renal Dialysis
Alzheimer Disease
Prospective Studies
Brain
Therapeutics
Serum Amyloid A Protein
Amino Acids
Renal Insufficiency

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Kitaguchi, Nobuya ; Hasegawa, Midori ; Ito, Shinji ; Kawaguchi, Kazunori ; Hiki, Yoshiyuki ; Nakai, Sigeru ; Suzuki, Nobuo ; Shimano, Yasunobu ; Ishida, Osamu ; Kushimoto, Hiroko ; Kato, Masao ; Koide, Sigehisa ; Kanayama, Kyoko ; Kato, Takashi ; Ito, Kengo ; Takahashi, Hiroshi ; Mutoh, Tatsuro ; Sugiyama, Satoshi ; Yuzawa, Yukio. / A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis : a potential therapeutic strategy for Alzheimer’s disease. In: Journal of Neural Transmission. 2015 ; Vol. 122, No. 11. pp. 1593-1607.
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abstract = "To obtain the proof of concept of a novel therapy for Alzheimer’s disease (AD), we conducted two prospective studies with hemodialysis patients who had amyloid β protein (Aβ) removed from their blood three times a week. One major pathological change in the brain associated with AD is Aβ deposition, mainly 40 amino acids Aβ1–40 and 42 amino acids Aβ1–42. Impaired Aβ clearance is proposed to be one cause of increased Aβ in the AD brain. Thus, we hypothesized that an extracorporeal removal system of Aβ from the blood may remove brain Aβ and be a useful therapeutic strategy for AD. In the first prospective study, plasma Aβ levels and the cognitive function of 30 hemodialysis patients (65–76 years old) were evaluated at baseline as well as 18 or 36 months after. Although plasma Aβ1–40 levels either decreased or remained unchanged, levels of Aβ1–42 either remained unchanged or increased at the second time point. Mini-Mental State Examination scores of most subjects increased or were maintained at the second time point. Aβ1–40 influx into the blood correlated with MMSE at the second time point. In the second prospective study, five patients (51–84 years old) with renal failure were evaluated before and after the initiation of hemodialysis. Plasma Aβ levels decreased, while cognitive function improved after initiating blood Aβ removal. Therefore, long-term hemodialysis, which effectively removes blood Aβ, might alter Aβ influx and help maintain cognitive function.",
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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 2015, 'A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis: a potential therapeutic strategy for Alzheimer’s disease', Journal of Neural Transmission, vol. 122, no. 11, pp. 1593-1607. https://doi.org/10.1007/s00702-015-1431-3

A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis : a potential therapeutic strategy for Alzheimer’s disease. / Kitaguchi, Nobuya; Hasegawa, Midori; Ito, Shinji; Kawaguchi, Kazunori; Hiki, Yoshiyuki; Nakai, Sigeru; Suzuki, Nobuo; Shimano, Yasunobu; Ishida, Osamu; Kushimoto, Hiroko; Kato, Masao; Koide, Sigehisa; Kanayama, Kyoko; Kato, Takashi; Ito, Kengo; Takahashi, Hiroshi; Mutoh, Tatsuro; Sugiyama, Satoshi; Yuzawa, Yukio.

In: Journal of Neural Transmission, Vol. 122, No. 11, 01.11.2015, p. 1593-1607.

Research output: Contribution to journalArticle

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T1 - A prospective study on blood Aβ levels and the cognitive function of patients with hemodialysis

T2 - a potential therapeutic strategy for Alzheimer’s disease

AU - Kitaguchi, Nobuya

AU - Hasegawa, Midori

AU - Ito, Shinji

AU - Kawaguchi, Kazunori

AU - Hiki, Yoshiyuki

AU - Nakai, Sigeru

AU - Suzuki, Nobuo

AU - Shimano, Yasunobu

AU - Ishida, Osamu

AU - Kushimoto, Hiroko

AU - Kato, Masao

AU - Koide, Sigehisa

AU - Kanayama, Kyoko

AU - Kato, Takashi

AU - Ito, Kengo

AU - Takahashi, Hiroshi

AU - Mutoh, Tatsuro

AU - Sugiyama, Satoshi

AU - Yuzawa, Yukio

PY - 2015/11/1

Y1 - 2015/11/1

N2 - To obtain the proof of concept of a novel therapy for Alzheimer’s disease (AD), we conducted two prospective studies with hemodialysis patients who had amyloid β protein (Aβ) removed from their blood three times a week. One major pathological change in the brain associated with AD is Aβ deposition, mainly 40 amino acids Aβ1–40 and 42 amino acids Aβ1–42. Impaired Aβ clearance is proposed to be one cause of increased Aβ in the AD brain. Thus, we hypothesized that an extracorporeal removal system of Aβ from the blood may remove brain Aβ and be a useful therapeutic strategy for AD. In the first prospective study, plasma Aβ levels and the cognitive function of 30 hemodialysis patients (65–76 years old) were evaluated at baseline as well as 18 or 36 months after. Although plasma Aβ1–40 levels either decreased or remained unchanged, levels of Aβ1–42 either remained unchanged or increased at the second time point. Mini-Mental State Examination scores of most subjects increased or were maintained at the second time point. Aβ1–40 influx into the blood correlated with MMSE at the second time point. In the second prospective study, five patients (51–84 years old) with renal failure were evaluated before and after the initiation of hemodialysis. Plasma Aβ levels decreased, while cognitive function improved after initiating blood Aβ removal. Therefore, long-term hemodialysis, which effectively removes blood Aβ, might alter Aβ influx and help maintain cognitive function.

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