The Ratio of Plasma Amyloid-β 1-42 over Serum Albumin Can Be a Novel Biomarker Signature for Diagnosing End-Stage Renal Disease-Associated Cognitive Impairment

Article type: Research Article

Authors: Hou, Yi-Chou^{a; b; c} | Chueh, Ti-I^d | Lu, Kuo-Cheng^{b; e} | Liu, Yi-Chien^{b; f} | Chen, Tso-Hsiao^c | Liu, Shing-Hwa^g | Chen, Ruei-Ming^{c; h; i; *}

Affiliations: [a] Department of Internal Medicine, Division of Nephrology, Cardinal Tien Hospital, New Taipei City, Taiwan | [b] School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan | [c] Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan | [d] Department of Medical Laboratory and Department of Education, Cardinal Tien Hospital, New Taipei City, Taiwan | [e] Department of Medicine, Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan | [f] Department of Neurology, Cardinal Tien Hospital, New Taipei City, Taiwan | [g] Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan | [h] Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan | [i] Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan

Correspondence: [*] Correspondence to: Ruei-Ming Chen, PhD, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing St., Taipei 11031, Taiwan. Tel.: +886 2 27361661 /Ext. 3222; Fax: +886 2 86621119; E-mail: rmchen@tmu.edu.tw.

Abstract: Background:Cognitive impairment (CI) is one of the major complications in chronic kidney disease patients, especially those with end-stage renal disease (ESRD). Limited biomarkers have been found that can significantly predict ESRD-associated cognitive decline. Objective:This cohort study aimed to investigate de novo biomarkers for diagnosis of the ESRD-associated CI. Methods:In this cohort study, qualified samples were divided into control (with an estimated glomerular filtration rate (eGFR) of≥60 mL/min and a Mini-Mental State Examination (MMSE) score of > 27), ESRD without CI (eGFR < 15 and MMSE > 27), and ESRD with CI (eGFR < 15 and MMSE < 27) groups. Levels of plasma amyloid-β (Aβ)1 - 42, serum indoxyl sulfate, and hematologic and biochemical parameters were measured. Results:Compared to the control group, levels of blood urea nitrogen, creatinine, and indoxyl sulfate were elevated in ESRD patients both without and with CI. Interestingly, ESRD patients with CI had the lowest levels of serum albumin. In contrast, levels of plasma Aβ1 - 42 were significantly higher in the ESRD with CI group than in the control and ESRD without CI groups. In addition, the ratio of plasma Aβ1 - 42 over serum albumin was significantly higher in the ESRD with CI group than in the control or ESRD without CI groups. Importantly, the area under the receiver operating characteristic curve (AUROC) for CI in the total population by the ratio of Aβ1 - 42 over albumin was 0.785 and significant (p < 0.05). Conclusions: This cohort study has shown that the ratio of plasma Aβ1 - 42 over serum albumin can be a de novo biomarker for the diagnosis and prognosis of ESRD-associated cognitive decline.

Keywords: Albumin, Alzheimer’s disease, amyloid-beta 1-42, biomarker signature, cognitive impairment, end-stage renal disease

DOI: 10.3233/JAD-230747

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1393-1405, 2024