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

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-ß and brain amyloid-ß deposition, which could contribute to elevated risk of dementia. OBJECTIVE: To investigate whether kidney impairment is associated with higher levels of circulating amyloid-ß and brain amyloid-ß 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-ß1 - 40 and amyloid-ß1 - 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-ß1 - 40 (standardized difference 0.12; 95% CI 0.09,0.14) and higher plasma amyloid-ß1 - 42 (0.08; 95% CI 0.05,0.10). Lower eGFR was associated with higher plasma amyloid-ß1 - 40 (0.36; 95% CI 0.33,0.39) and higher amyloid-ß1 - 42 (0.32; 95% CI 0.29,0.35). CONCLUSION: Low clearance of amyloid-ß 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.