Blood-based biomarkers for Alzheimer’s disease: influence of kidney function

Blood-based biomarkers are increasingly incorporated into the diagnostic work-up of Alzheimer’s disease (AD). Systemic conditions such as kidney dysfunction (KD) may influence their plasma concentrations and complicate clinical interpretation. While the association between KD and blood AD biomarkers has been previously reported, practical strategies to mitigate this effect has not been defined. For these reasons, we evaluated the impact of KD on plasma levels of phosphorylated tau (p-Tau217, p-Tau181), amyloid-β (Aβ42/Aβ40), and neurofilament light chain (NfL), and developed correction strategies. We retrospectively selected 112 individuals (52 with AD, 21 with other neurodegenerative diseases, and 39 with non-neurodegenerative conditions) with available CSF AT biomarker profiles and paired plasma samples, all with documented abnormal renal function within one year from sampling. Plasma p-Tau217, p-Tau181, Aβ42/Aβ40, and NfL were measured on a fully automated chemiluminescent immunoassay platform (Lumipulse). Creatinine was re-measured on serum samples collected together with plasma samples to ensure temporal correspondence between kidney function and biomarker assessments. KD was defined as eGFR < 60 mL/min/1.73 m². We assessed the impact of KD on plasma biomarkers and evaluated correction strategies based on serum creatinine and eGFR, using CSF biomarkers as a biological reference. KD was associated with higher plasma concentrations of p-Tau217, p-Tau181, Aβ42, Aβ40, and NfL, not with the Aβ42/Aβ40 ratio. Creatinine- and eGFR-based correction improved the correlation between plasma and CSF NfL. For AD classification, plasma p-Tau217 showed the highest diagnostic accuracy (AUC: 0.955, 95% CI: 0.920–0.990), with creatinine correction resulting in a numerical but not statistically significant improvement (AUC: 0.965, 95% CI 0.937–0.993), whereas a modest, not significant, increase in performance was observed for p-Tau181 after correction (AUC from 0.830, 95% CI: 0.752–0.907; to 0.862, 95% CI: 0.790–0.933). Corrected p-Tau cut-offs closely aligned with those previously reported in cohorts without KD. KD alters plasma biomarker concentrations. Correction for renal function may be particularly relevant in individuals with moderate-severe KD and may facilitate the application of established plasma biomarker cut-offs derived from cohorts without KD.