Abstract
Amyloid-beta (Aβ) plays a central role in the pathogenesis of Alzheimer’s disease (AD), and it is a major therapeutic target for AD. It is proposed that removal of Aβ in blood can facilitate Aβ clearance from the brain, representing a promising therapeutic approach for AD. However, the efficacy and mechanisms for Aβ clearance by peripheral organs and tissues remain largely unknown. In the present study, 47 chronic kidney disease (CKD) patients (16 newly diagnosed patients who had never been dialyzed and 31 patients who were receiving dialysis) and 43 normal controls (NC) were enrolled. We found that serum Aβ levels were significantly higher in CKD patients than NC. CKD patients who were receiving dialysis had lower serum Aβ levels than patients without receiving dialysis, being comparable to NC. Furthermore, serum Aβ levels were correlated with renal functions reflected by estimated glomerular filtration rate (eGFR) and residual GFR (rGFR). Our study suggests that kidney is involved in peripheral clearance of Aβ, and dialysis might be a potential therapeutic approach of Aβ removal.
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References
Coresh J et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298(17):2038–2047
James BD et al (2014) Contribution of Alzheimer disease to mortality in the United States. Neurology 82(12):1045–1050
Lemere CA et al (2003) Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice. Neurobiol Dis 14(1):10–18
Liu YH, et al (2014) Clearance of Amyloid-Beta in Alzheimer's Disease: Shifting the Action Site from Center to Periphery. Mol Neurobiol
Wang YJ (2014) Alzheimer disease: Lessons from immunotherapy for Alzheimer disease. Nat Rev Neurol 10(4):188–189
Liu YH et al (2012) Immunotherapy for Alzheimer disease: the challenge of adverse effects. Nat Rev Neurol 8(8):465–469
Miwa K et al (2014) Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease. Neurology 82(12):1051–1057
Li J et al (2011) Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology 76(17):1485–1491
Levey AS et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612
Hoek FJ et al (2007) Estimation of residual glomerular filtration rate in dialysis patients from the plasma cystatin C level. Nephrol Dial Transplant 22(6):1633–1638
Wang YJ, Zhou HD, Zhou XF (2006) Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives. Drug Discov Today 11(19–20):931–938
Ghiso J et al (1997) Alzheimer's soluble amyloid beta is a normal component of human urine. FEBS Lett 408(1):105–108
Arvanitakis Z et al (2002) Serum creatinine levels correlate with plasma amyloid Beta protein. Alzheimer Dis Assoc Disord 16(3):187–190
Delaney MP et al (2008) Relationship of serum cystatin C to peritoneal and renal clearance measures in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis 51(2):278–284
Helmer C et al (2011) Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology 77(23):2043–2051
Bradshaw EM et al (2013) CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat Neurosci 16(7):848–850
Sehgal N et al (2012) Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci U S A 109(9):3510–3515
Liu Y et al (2010) Circulating neprilysin clears brain amyloid. Mol Cell Neurosci 45(2):101–107
Henderson SJ et al (2014) Sustained peripheral depletion of amyloid-beta with a novel form of neprilysin does not affect central levels of amyloid-beta. Brain 137(Pt 2):553–564
Walker JR et al (2013) Enhanced proteolytic clearance of plasma Abeta by peripherally administered neprilysin does not result in reduced levels of brain Abeta in mice. J Neurosci 33(6):2457–2464
Acknowledgments
This work was supported by the National Natural Science Foundation of China (30973144), PLA healthcare research grant (13BJZ31), Chinese postdoctor scientific grant (2013 T60955) and Chongqing postdoctor research grant (XM201342).
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Yu-Hui Liu and Yang Xiang contributed equally to this work.
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Liu, YH., Xiang, Y., Wang, YR. et al. Association Between Serum Amyloid-Beta and Renal Functions: Implications for Roles of Kidney in Amyloid-Beta Clearance. Mol Neurobiol 52, 115–119 (2015). https://doi.org/10.1007/s12035-014-8854-y
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DOI: https://doi.org/10.1007/s12035-014-8854-y