The Association of Kidney Function with Plasma Amyloid-β 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-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-β 1 - 40 and amyloid-β 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 m2 lower eGFR: 1.08; 95% CI: 0.95,1.23). A doubling of ACR was associated with a higher level of plasma amyloid-β 1 - 40 (standardized difference: 0.12; 95% CI: 0.09,0.14) and higher plasma amyloid-β 1 - 42 (0.08; 95% CI: 0.05,0.10). Lower eGFR was associated with higher plasma amyloid-β 1 - 40 (0.36; 95% CI: 0.33,0.39) and higher amyloid-β 1 - 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.

Research trends and hotspots of glial fibrillary acidic protein within the area of Alzheimer’s disease: a bibliometric analysis

“…Furthermore, it is important to evaluate the effects of clinical confounders and biological factors on the clinical diagnostic and prognostic performance of GFAP for AD (Hansson et al, 2022). Previous studies preliminarily found that impaired kidney function could affect the concentration of amyloid 1-42, p-tau181, and NfL but not plasma GFAP (Sedaghat et al, 2023;Zhang et al, 2023); however, more comprehensive studies with larger cohorts are still needed to explore the effect of more factors, such as peripheral neuropathies and body mass index, on blood GFAP for more accurate laboratory measurements and clinical interpretation (Hansson et al, 2022). By this bibliometric analysis, it was also found that the USA, China, England, Japan, Spain, Germany, and Sweden contributed the most research on GFAP within the area of AD.…”

Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant

“…Previous studies have indicated higher AD biomarker levels in CKD without clear association with cerebral amyloid deposition. 30 , 32 Thus, elevated AD biomarker levels in CKD may be due to lower elimination of these biomarkers by the kidneys rather than improvement in cerebral amyloid pathology. Although we did not evaluate cerebral amyloid in this study, it is hard to imagine a near complete resolution of amyloid deposits in a 12‐week period.…”

Amyloid-β and caspase-1 are indicators of sepsis and organ injury

“…ICU patients frequently develop post-ICU syndrome with a spectrum of chronic cognitive impairments reminiscent of AD; the persistent elevations of Aβx-40 plasma level in both ICU cohorts observed at time of admission to 7 days later may be a contributing factor. Considering that Aβx-40 has been shown to be the primary form of soluble Aβ excreted in urine [ 52 ], it will be important for future studies to determine whether increasing Aβx-40 plasma levels are due to a shift in excretion caused by kidney dysfunction. Of additional interest, sepsis causes long-lasting, trained innate immunity that increases Aβ-induced cognitive impairments in mice [ 53 ].…”