Potential therapeutic system for Alzheimer's disease: removal of blood Aβs by hemodialzyers and its effect on the cognitive functions of renal-failure patients.
The pathological changes of Alzheimer's disease include the deposition of amyloid β protein (Aβ) as senile plaques in the brain. We hypothesized that the rapid removal of Aβs from the blood may act as a peripheral Aβ drainage sink from the brain. In this study, the plasma Aβ concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 ± 3.8 years), 26 renal-failure patients without hemodialysis (66.6 ± 14.7 years), and 17 age-matched healthy controls (66.6 ± 4.1 years). The concentrations of plasma Aβs increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of Aβ(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed Aβs in the blood during hemodialysis sessions. The plasma Aβ concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of Aβs removed during a hemodialysis session was calculated to be comparable to the Aβs dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing Aβs from the blood is worthy of further investigation, including whether or not Aβs in the brain decrease.
Department of Nephrology, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
Masao
M
Kato
Kazunori
K
Kawaguchi
Sigeru
S
Nakai
Kazutaka
K
Murakami
Hideo
H
Hori
Atsushi
A
Ohashi
Yoshiyuki
Y
Hiki
Shinji
S
Ito
Yasunobu
Y
Shimano
Nobuo
N
Suzuki
Satoshi
S
Sugiyama
Hiroshi
H
Ogawa
Hiroko
H
Kusimoto
Tatsuro
T
Mutoh
Yukio
Y
Yuzawa
Nobuya
N
Kitaguchi
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000097:blood*; D003072:Cognition Disorders / Q000150:complications / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D009483:Neuropsychological Tests; D006435:Renal Dialysis
D016229:Amyloid beta-Peptides