Creatinine and body mass index influence on plasma amyloid ratio, p‐tau217 and neurofilament light

Abstract

AbstractBackgroundWith the advent of blood‐based biomarkers, it is important to consider whether measurements of such markers are affected by factors related to blood filtration or volume. Previous studies suggested that amyloid‐beta (Aβ) and neurofilament light (NfL) measured in blood are related to creatinine levels. Here we first investigated whether creatinine and body mass index (BMI) were related to various blood‐based biomarkers, and then evaluated whether these markers affected the associations between plasma and cerebrospinal fluid (CSF), or conversion to dementia.MethodParticipants with plasma, CSF, creatinine, and BMI data from BioFinder1 (n=748) and BioFinder2 (n=560) cohort were included in the study and analyzed separately (Table 1). In both cohorts, the plasma and CSF biomarkers of interest were Aβ42/Aβ40, p‐tau217, and NfL. Linear regression models were first used to assess plasma associations with BMI and creatinine. Subsequent models compared whether plasma estimates predicting corresponding CSF levels or conversion to dementia within a 4‐year period (BioFinder1 only) were improved if creatine and BMI were added as covariates.ResultIn both cohorts, creatinine levels were positively correlated with plasma p‐tau217 and NfL, while BMI was negatively correlated with the same markers. No associations were found with the Aβ42/Aβ40 ratio (Table 2). In both cohorts, looking at plasma‐CSF associations, plasma NfL coefficients were significantly higher in models including creatinine and BMI as covariates, but plasma p‐tau217 coefficients were unchanged (Figure 1). For Aβ42/Aβ40, only in BioFinder2 was the plasma estimate higher with creatinine and BMI as covariates. In BioFinder1, where longitudinal data was available, plasma p‐tau217 and NfL estimates were somewhat higher in discriminating participants who developed AD or any cause dementia respectively when including creatinine and BMI as covariates (Figure 2; AUC change of only 0.01).ConclusionIn two cohorts covering the full spectrum of AD, creatinine and BMI were related to plasma levels of almost all markers. BMI and creatinine improved some plasma estimates of associations with the CSF counterparts and conversion to dementia, but to a low magnitude. Although creatinine and BMI relate to plasma levels, the clinical relevance of including such factors seems to be minor.