The Association of Kidney Function with Plasma Amyloid-β Levels and Brain Amyloid Deposition
Article type: Research Article
Authors: Sedaghat, Sanaza; * | Ji, Yuekaia | Hughes, Timothy M.b | Coresh, Josefc | Grams, Morgan E.c | Folsom, Aaron R.a | Sullivan, Kevin J.d | Murray, Anne M.e; f | Gottesman, Rebecca F.g | Mosley, Thomas H.d | Lutsey, Pamela L.a
Affiliations: [a] Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA | [b] Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA | [c] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA | [d] Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA | [e] Department of Medicine, Geriatrics Division, Hennepin Health Care, and Hennepin Health Care Institute, Minneapolis, MN, USA | [f] Department of Medicine, University of Minnesota, Minneapolis, MN, USA | [g] National Institute of Neurological Disorders and Stroke Intramural Research Program, NIH, Bethesda, MD, USA
Correspondence: [*] Correspondence to: Sanaz Sedaghat, PhD, University of Minnesota, Division of Epidemiology and Community Health, 1300 S. 2nd St., Suite 300, Minneapolis, MN 55454, USA. Tel.: +1 612 626 8568; E-mail: sedaghat@umn.edu.
Abstract: Background:Reduced kidney function is related to brain atrophy and higher risk of dementia. It is not known whether kidney impairment is associated with higher levels of circulating amyloid-β and brain amyloid-β deposition, which could contribute to elevated risk of dementia. Objective:To investigate whether kidney impairment is associated with higher levels of circulating amyloid-β and brain amyloid-β deposition. Methods:This cross-sectional study was performed within the community–based Atherosclerosis Risk in Communities (ARIC) Study cohort. We used estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C levels and urine albumin-to-creatinine ratio (ACR) to assess kidney function. Amyloid positivity was defined as a standardized uptake value ratios > 1.2 measured with florbetapir positron emission tomography (PET) (n = 340). Plasma amyloid-β1 - 40 and amyloid-β1 - 42 were measured using a fluorimetric bead-based immunoassay (n = 2,569). Results:Independent of demographic and cardiovascular risk factors, a doubling of ACR was associated with 1.10 (95% CI: 1.01,1.20) higher odds of brain amyloid positivity, but not eGFR (odds ratio per 15 ml/min/1.73 m2 lower eGFR: 1.08; 95% CI: 0.95,1.23). A doubling of ACR was associated with a higher level of plasma amyloid-β1 - 40 (standardized difference: 0.12; 95% CI: 0.09,0.14) and higher plasma amyloid-β1 - 42 (0.08; 95% CI: 0.05,0.10). Lower eGFR was associated with higher plasma amyloid-β1 - 40 (0.36; 95% CI: 0.33,0.39) and higher amyloid-β1 - 42 (0.32; 95% CI: 0.29,0.35). Conclusion:Low clearance of amyloid-β and elevated brain amyloid positivity may link impaired kidney function with elevated risk of dementia. kidney function should be considered in interpreting amyloid biomarker results in clinical and research setting.
Keywords: Albuminuria, amyloid, glomerular filtration rate, kidney, kidney function, plasma amyloid-β, positron emission tomography
DOI: 10.3233/JAD-220765
Journal: Journal of Alzheimer's Disease, vol. 92, no. 1, pp. 229-239, 2023
