The Association of Kidney Function with Plasma Amyloid-β Levels and Brain Amyloid Deposition

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-beta and brain amyloid-beta deposition, which could contribute to elevated risk of dementia. Objective: To investigate whether kidney impairment is associated with higher levels of circulating amyloid-beta and brain amyloid-beta 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-beta(1-40) and amyloid-beta(1-42) 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 m(2) lower eGFR: 1.08; 95%CI: 0.95,1.23). A doubling of ACR was associated with a higher level of plasma amyloid-beta(1-40) (standardized difference: 0.12; 95%CI: 0.09,0.14) and higher plasma amyloid-beta(1-42) (0.08; 95%CI: 0.05,0.10). Lower eGFR was associated with higher plasma amyloid-beta(1-40) (0.36; 95%CI: 0.33,0.39) and higher amyloid-beta(1-42) (0.32; 95%CI: 0.29,0.35). Conclusion: Low clearance of amyloid-beta 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.