A-40: Associations of Alzheimer’s Plasma Biomarkers with Kidney Disease Functioning

Abstract

Objective: Plasma concentrations of amyloid-beta 42/40 (Aβ42/40) and phosphorylated tau 217 (p-tau217) are now routinely ordered clinically in older adults as proxy markers for brain Aβ pathology in Alzheimer’s disease. Marked kidney impairment in chronic kidney disease (CKD) influences Aβ42/40 and p-tau217 measurements; however, the relationship between these plasma biomarker titers and subclinical, age-related kidney function across the estimated glomerular filtration rate (eGFR) dynamic range remains less clear. We tested in older adults the relationship between lower eGFR and higher p-tau217, as well as lower Aβ42/40. Method/Data Selection: Plasma Aβ42/40 and p-tau217 levels were measured using the LumiPulse immunoassay in 33 cognitively-intact older adults, aged 63-81 years. eGFR was quantified with a blood laboratory test. Protein values were log-transformed, and linear regression analyses examined the association between each biomarker and eGFR. Covariates (age, sex, education) were entered, with an alpha level of 0.05. Results/Data Synthesis: eGFR values ranged from 45-109 (mean=80.85, SD=14.10), while Aβ42/40 levels were between .014-.107 (mean=.085, SD=.016) and p-tau217 levels between .030-.329 (mean=.088, SD=.070). Lower eGFR was significantly associated with higher p-tau217 (b=-.02, SE=.01, p=.003, R2=.47), but not Aβ42/40 (b=-.01, SE=.01, p=.128, R2=.14). After excluding 9% of participants with eGFR< 60, the association for p-tau217 remained significant (p=.010), and an inverse association emerged for Aβ42/40 (b=-.01, SE=.01, p=.021, R2=.24). Conclusions: Lower kidney function, measured by eGFR, was associated with higher p-tau217 over the eGFR dynamic range. An association was observed for Aβ42/40 after excluding participants with clinically significant low eGFR. Blood-based Alzheimer’s biomarkers will likely need to incorporate an eGFR-related adjustment with further research to better guide clinical interpretations.