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

Article type: Research Article

Authors: Kitaguchi, Nobuya^{a; *} | Tatebe, Harutsugu^b | Sakai, Kazuyoshi^a | Kawaguchi, Kazunori^a | Matsunaga, Shinji^c | Kitajima, Tomoko^c | Tomizawa, Hiroshi^d | Kato, Masao^e | Sugiyama, Satoshi^{e; 1} | Suzuki, Nobuo^f | Mizuno, Masao^d | Takechi, Hajime^g | Nakai, Shigeru^a | Hiki, Yoshiyuki^{a; 2} | Kushimoto, Hiroko^h | Hasegawa, Midori^e | Yuzawa, Yukio^e | Tokuda, Takahikoⁱ

Affiliations: [a] Faculty of Clinical Engineering, School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan | [b] Department of Zaitaku (Homecare) Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan | [c] Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan | [d] Mizuno Clinic, Toyoake, Aichi, Japan | [e] Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan | [f] Chiryu Clinic, Chiryu, Aichi, Japan | [g] Department of Geriatrics and Cognitive Disorders, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan | [h] Nishichita General Hospital, Tokai, Aichi, Japan | [i] Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan

Correspondence: [*] Correspondence to: Nobuya Kitaguchi, PhD, Faculty of Clinical Engineering, School of Health Sciences, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan. Tel.: +81 562 93 2657; Fax: +81 562 93 4595; E-mail: nkitaguc@fujita-hu.ac.jp.

Note: [1] Present address: Kanayama Clinic, Nagoya, Aichi, Japan.

Note: [2] Present address: Narumi Clinic, Nagoya, Aichi, Japan.

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 1 h 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.

Keywords: Alzheimer’s disease, amyloid-β peptide, blood component removal, hemodialysis, tau protein

DOI: 10.3233/JAD-190087

Journal: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 687-707, 2019