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

• Published in: Journal of Neural Transmission 2015-11, Vol.122 (11), p.1593-1607
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - therapy; Amyloid beta-Peptides - blood; Brain - diagnostic imaging; Brain - metabolism; Cognition - physiology; Cognition Disorders - blood; Cognition Disorders - diagnostic imaging; Cognition Disorders - therapy; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - diagnostic imaging; Kidney Failure, Chronic - therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neurology; Neurology and Preclinical Neurological Studies - Original Article; Neurosciences; Peptide Fragments - blood; Positron-Emission Tomography; Prospective Studies; Psychiatry; Renal Dialysis; Smoking - blood; Smoking - psychology; Tomography, X-Ray Computed; Treatment Outcome
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-015-1431-3

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 Aβ 1–40 and 42 amino acids Aβ 1–42 . 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 Aβ 1–40 levels either decreased or remained unchanged, levels of Aβ 1–42 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. Aβ 1–40 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.