Alzheimer’s Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults

Abstract

AbstractImportanceRecent Alzheimer’s disease (AD) clinical trials have used Cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests Alzheimer’s Disease (AD) risk may be related to impaired renal function but the association of variation in levels of commonly used AD biomarkers with kidney function are unknown.ObjectiveTo investigate the association between estimated glomerular filtration rate (eGFR), CSF levels of AD biomarkers: amyloid beta1–42 (Aβ42), Tau or phosphorylated Tau181 (pTau).Design, Setting, and ParticipantsWe conducted an analysis using data from participants enrolled in two research protocols at the Goizueta Alzheimer’s Disease Research Center that had simultaneous measurements of serum creatinine at the time of their Cerebrospinal fluid (CSF) collection (N=973). The participants had a mean age of 66.52 years, 23.33% were African American, and 63% were women, with 42.46% having mild cognitive impairment (MCI). The estimated glomerular filtration rate (eGFR) was obtained from chronic kidney disease Epidemiology Collaboration. All participants had similar CSF collection procedures. Aβ42, Tau or pTau were measured on the Luminex ALZBIO platform. General linear models and individual data were used to assess relationships between biomarkers and eGFR.ResultsLower eGFR was associated with lower Aβ42/Tau ratio (slope= 0.033 units, p<0.0001) and Aβ42 (slope=0.75, p=0.002) and higher Tau (slope= -0.39, p<0.0001) and pTau (slope= -0.13, p=0.0002). Although these associations remained significant after adjusting for cognitive status, we observed interactions between MCI and eGFR. This interaction revealed that the impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (interaction MCI*GFR p-values were 0.005 for Ab42, 0.04 for tau and pTau, and 0.05 for the ratio).ConclusionWe found a significant association between eGFR with CSF AD-biomarkers that may differ by cognitive status. This suggests that kidney function should be considered both in the context of interpreting AD biomarkers as well as exploring potential systemic factors that may increase risk of AD. Future longitudinal studies need to further explore the impact of kidney function on the pathogenesis of AD and related Biomarkers.KEY POINTSQuestionAre Cerebrospinal Fluid (CSF)AD-biomarker measurements impacted by kidney function?FindingsIn this analysis of data from 973 individuals who had both cerebrospinal fluid (CSF) AD-biomarkers (Aβ42, Tau, and pTau181) and kidney function measurements, there were significant associations between estimated glomerular filtration rate (eGFR) and measures of CSF AD-biomarkers. These associations were more pronounced in those with cognitive impairment.MeaningKidney function may have a significant impact on AD-biomarker measurements in the CSF, especially in those in the early symptomatic stages of AD.